A direct follow-up to Heretics of Dune, the novel chronicles the continued struggles of the Bene Gesserit sisterhood against the violent Honored Matres, who are succeeding in their bid to seize control of the universe and destroy the factions and planets that oppose them.

Chapterhouse: Dune ends with a cliffhanger, and Herbert's subsequent death in 1986 left some overarching plotlines of the series unresolved.

The Matres are seeking to assimilate the technology and superhuman skills of the Bene Gesserit, and exterminate the Sisterhood itself.

Now in command of the Bene Gesserit, Mother Superior Darwi Odrade continues to develop her drastic, secret plan to overcome the Honored Matres.

The Honored Matres have also destroyed the entire Bene Tleilax civilization, with Tleilaxu Master Scytale the only one of his kind left alive.

In Bene Gesserit captivity, Scytale possesses the Tleilaxu secret of ghola production, which he has reluctantly traded for the Sisterhood's protection.

Lucilla is forced to land on Gammu where she seeks refuge with an underground group of Jews.

Before doing so, he reveals Rebecca, a "wild" Reverend Mother who has gained her Other Memory without Bene Gesserit training.

Lucilla shares minds with Rebecca, who promises to take the memories of Lampadas safely back to the Sisterhood.

From this, Lucilla deduces that the greater enemy that the Matres are fleeing from is making extensive use of biological warfare.

Back on Chapterhouse, Odrade confronts Duncan and forces him to admit that he is a Mentat, proving that he retains the memories of his many ghola lives.

Teg uses his secret ability to see no-ships to secure control of the system, and victory for the Bene Gesserit seems inevitable.

Odrade, however, had planned for the possible failure of the Bene Gesserit attack and left Murbella instructions for a last desperate gamble.

Murbella pilots a small craft down to the surface, announcing herself as an Honored Matre who, in the confusion, has managed to escape the Bene Gesserit with all their secrets.

[4] Gerald Jonas of The New York Times noted that "Against all odds, the universe of Dune keeps getting richer in texture, more challenging in its moral dilemmas.

"[5] Dave Langford reviewed the novel for White Dwarf #65, and stated that "The hyper-acute characters are impressive, the resolution thoughtful and humane.

Though initially I gave up after Children, Heretics and Chapter House have partially Restored My Faith.

Brian was cleaning out his garage to make an office space and he found all these boxes that had 'Dune Notes' on the side.

Anderson said that Frank Herbert's notes included a description of the story and a great deal of character background information.