In 1348, the inhabitants of Cambridge live under the shadow of a terrible pestilence that has ravaged Europe and is traveling relentlessly toward England. Physician Matthew Bartholomew, however, is distracted by the sudden and inexplibable death of the Master of Michaelhouse - a death the university authorities do not want investigated. When three more scholars die in mysterious circumstances, Bartholomew defies the university and begins his own inquiry. His pursuit for the truth leads him into a complex tangle of lies and intrigue and causes him to question the innocence of his closest friends, and even his family.

When the Black Death finally arrives and sweeps through the town, Bartholomew's theories of a dark and sinister conspiracy are swiftly replaced by a desperate struggle for personal survival. But for some, even the dangers of a horrifying death from the bubonic plague are secondary to gaining wealth and power, and Bartholomew is dragged deeper and deeper into a quagmire of deceit that threatens not only his life, but also the continued existence of the university and the town.