The resources of Earth have been depleted, and humanity has moved to another star system and terraformed many of the planets. All the planets are controlled by the supposedly peace-loving yet still rather authoritarian Alliance. But a frontier justice still holds sway farther from the "core planets", where outlaws like the crew of Serenity can scrape out a living if they keep clear of Alliance forces and the Reavers, savage and cannibalistic humans who dwell beyond the outer planets and raid the Alliance worlds around the rim.
In order to earn her continued passage onboard Serenity, a fugitive from the Alliance, the telepathic River Tam (Summer Glau), accompanies Captain Malcolm Reynolds (Nathan Fillion), Jayne (Adam Baldwin), and Zoë (Gina Torres) on a mission to steal the payroll of an outer planet security company financed by the Alliance. During the robbery, the crew narrowly avoids capture by a Reaver raiding party when River is able to telepathically sense their approach. Wash (Alan Tudyk), the ship's pilot (and Zoë's husband) brings the ship to intercept the crew's surface vehicle, saving the crew from a grisly fate.
River (Summer Glau) attacking people in the bar.River's brother Simon (Sean Maher), the crew's doctor, angrily reacts to the captain's willingness to put his younger sister in such grave danger. Captain Reynolds responds by suggesting they leave at the next planet they land on, Beaumonde, where the crew expects to sell their loot. Simon agrees to the arrangement. The Tams do indeed disembark at Beaumonde, but while the captain haggles with the buyers, River suddenly starts attacking people in the same bar that the captain and Jayne are patronizing. Despite being a 90 pound (41 kg) girl, she manages to incapacitate everyone, including Jayne, and is about to shoot Captain Reynolds when Simon arrives and shouts a phrase in Russian, causing her to fall asleep.
Simon explains to the captain that, during her captivity by the Alliance, she was trained and conditioned to become an assassin. The only thing that can stop her after this conditioning has been triggered is the "safe-word" he uttered. Despite knowledge of this new danger and his anger at not being told about the possibility of carrying a potential living weapon, the captain allows Simon and River to continue traveling on Serenity.
The crew contacts Mr. Universe (David Krumholtz), a reclusive techno-geek who dwells with his robotic wife on a planet surrounded by an opaque ion cloud. After watching the security camera footage of the bar on Beaumonde, Mr. Universe discovers that River's outburst was triggered by a subliminal message in a seemingly harmless cartoon advertisement that had been broadcast all over the Alliance during the previous weeks. He tells the crew that before her attack, River had whispered the name "Miranda." He also notes that the footage has been viewed by someone else with high Alliance clearance.
Fearing Alliance pursuit, the crew takes refuge in the Haven mining colony with Shepherd Book (Ron Glass), a priest who once traveled with Serenity's crew. Book warns Mal that the Alliance agent pursuing River is likely to be an "Operative," and very dangerous. Shortly thereafter, the captain receives a call from Inara (Morena Baccarin), another former passenger. Their conversation is awkward but pleasant enough — with no arguing — leading Mal and Zoe to the conclusion that it's a trap, but they decide to visit Inara anyway. Mal's fears are realized; Inara is held hostage by a ruthless and nameless Operative (Chiwetel Ejiofor). The Operative offers to let the captain go on his way if he turns River over to him, but thanks to Inara's quick thinking, she and the captain escape the Operative and return to Serenity, which takes off undetected.
Another of River's outbursts shows the crew the meaning of "Miranda". It is the name of an outer rim planet, which had once been inhabited but was thought to be wiped out in a terraforming accident. River had subconsciously learned something mysterious about the planet when she came in telepathic contact with a member of the Alliance Parliament during her training. Traveling to Miranda to learn more would require crossing through what is now Reaver territory, which the crew members agree would be suicide, so instead Serenity returns to Haven and Shepherd Book.
On arrival, however, the crew discovers that the outpost has been ravaged by Alliance forces, and its inhabitants killed. Mal finds Book, who has shot down the attacking ship. However, he has been mortally wounded and dies in Mal's arms. Several other outposts that had harbored Serenity in the past have also been destroyed. Captain Reynolds receives a message from the Operative claiming responsibility, and promising more of the same until River is turned over.
Mal (Nathan Fillion) ordering the crew to remodel Serenity to look like a Reaver ship.Mal comes out and orders that Serenity be remodelled to look like a Reaver ship, which involves warpainting and mutilating the hull, making a dangerous modification to the engine, arming the weaponless cargo vessel with the settlers' cannon and tying bodies of the dead settlers to the prow. Everyone protests, but Mal furiously informs them that they can either do what he says or leave the ship now.
Serenity, now painted red and looking far more menacing, leaves for Miranda. The ship moves through a whole mass of Reaver vessels, and after an agonising wait, finally reaches the other side without incident.
Upon reaching Miranda, the crew discovers a normal, terraformed planet, with an earth-like environment which is completely habitable. The strange part is that the sprawling cities that dot the planet's surface are empty. Inside the buildings and cars are badly decomposed corpses, with no apparent cause of death. There are no signs of violence or disease. It is as if the people simply died.
The crew discover a log recorded by an Alliance research and rescue team after the disaster. The log recounts what has happened: the Alliance administered the chemical substance G-23 paxilon hydrochlorate, or simply "Pax", to the populace. It was supposed to remove aggression and thus render the planet free of violence. An unfortunate side effect was that the populace had stopped working, or eating, or caring about anything. They simply gave up on life and died in their newfound nonaggressive state. However, there was a small minority of the populace (approximately a tenth of a percent, thus given the planet's original population of 30,000,000 approximately 30,000 individuals) for which the drug had the opposite effect. They became extremely aggressive and mentally unstable, mutilating their own bodies, and killing the researchers who had come to investigate. They eventually left the planet and formed into the much feared Reavers. Thus, the Alliance was actually responsible for the creation of this menace...
