[1] The series chronicles the fictional Butlerian Jihad, a crusade by the last free humans in the universe against the thinking machines, a violent and dominating force led by the sentient computer Omnius.
After first being suggested by the traitor Yorek Thurr, an RNA retrovirus is designed by the captured Tlulaxa Rekur Van and the independent robot Erasmus.
Gathering the bulk of the machine armies stationed at the different synchronized planets, the evermind launches the massive fleet towards the League capital Salusa Secundus.
After learning of the imminent destruction headed their way in the form of the machine fleet, Vorian Atreides formulates a plan whereby the humans can launch pulse-atomic attacks on all of the undefended Synchronized Worlds, ridding the universe of Omnius altogether.
However, this plan called for the use of the still unreliable space-folding technology in order to carry out the attacks before the machines have a chance to recall the fleet en route to Salusa.
Each time the human armies fold space to a new location there is a 10% attrition rate due to the undependable space-folders because of the uncertainty principle.
Omnius, again at the suggestion of Thurr, sends machines with primitive minds that can evade the scrambler network to attack Salusa Secundus and Rossak.
Claiming to have had a vision of Serena Butler herself (possibly a hallucination caused by her illness), Rayna begins smashing anything resembling thinking machines, including even innocuous devices, and desperately needed medical equipment.
A new group known as the Martyrists who worship The Three Martyrs: Serena Butler, Manion the Innocent, and Iblis Ginjo, are instantly taken up by Rayna's mission.
The primary commandment in the Orange Catholic Bible, "thou shall not make a machine in the likeness of a human mind" is attributed directly to Rayna Butler.
While surveying Wallach IX, which has been devastated during the Great Purge, for possible survivors in need of aid, Primero Quentin Butler (Faykan and Abulurd Harkonnen's father) is captured by cymeks, and taken to the Titan stronghold on Hessra.
In a final attempt to save the captives, Abulurd deactivates the weapons for the entire fleet, making the Corrin attack more difficult and dangerous and eventually causing much higher casualties.
The Sorceresses of Rossak take their final steps toward becoming the Bene Gesserit sisterhood when a resurgence of the machine plague occurs after the Great Purge.
Paranoid and feeling that the doctor might somehow usurp her power, the leader of the Sorceresses, Ticia Cenva, poisons Raquella with the Rossak drug.
[4] After the Butlerian Jihad, Raquella assumes authority over the Sorceresses of Rossak and their breeding programs and founds the Bene Gesserit school of thought.
After the situation on Rossak is resolved, Mohandas Suk sets out on his mission to "form a medical school like none the League has ever seen".
Determined to find a solution to the space-folding problem, Norma Cenva experiments on herself by sealing herself inside a tank filled with gaseous melange.
When Gilbertus sneaks onto one of the cargo haulers of the Bridge of Hrethgir containing a Serena Butler clone with whom he is infatuated, Erasmus disables the explosive trip mechanism in order to save him.