A new civilization has risen, with three dominant powers: the Ixians, whose no-ships are capable of piloting between the stars and are invisible to outside detection; the Bene Tleilax, who have learned to manufacture spice in their axlotl tanks and have created a new breed of Face Dancers; and the Bene Gesserit, a matriarchal order of subtle political manipulators who possess superhuman abilities.

The most powerful of these forces are the Honored Matres, a violent society of women bred and trained for combat and the sexual control of men.

The Bene Gesserit leader, Mother Superior Taraza, brings Mentat and former Supreme Bashar Miles Teg out of retirement to oversee the protection of their latest Tleilaxu-provided Duncan Idaho ghola on the planet Gammu.

She also sends Bene Gesserit Imprinter Lucilla to instruct Duncan, and eventually bind his loyalty to the Sisterhood with her sexual talents.

At the same time, Teg's biological daughter, Reverend Mother Darwi Odrade, is put in command of the Bene Gesserit keep on Rakis.

Teg is tortured by a T-Probe, but under pressure discovers new abilities: drastically increased physical capabilities and an uncertain type of prescience, which he uses to easily escape.

Teg leads his troops in a suicidal defense of Rakis designed to enrage the Honored Matres and goad them into using their planet-destroying Obliterators.