Hyperpyrexia, defined as temperature elevation of at least 106 degrees F, is generally thought to be infrequently associated with infection. In a 3-year retrospective analysis of 39 episodes of hyperpyrexia in adults, 94% of cases were associated with infection. In 35 patients (90%) the causes were potentially treatable, and the majority were associated with common bacteria or fungi. Fourteen (36%) patients were bacteremic. Fifteen (43%) of those with treatable infections had additional noninfectious reasons for hyperpyrexia. Only three patients died in conjunction with hyperpyrexia, and none of these had treatable infection. Infection must be strongly considered by the clinician faced with a hyperpyrexic patient. Antimicrobial therapy is indicated in the majority of cases, and most patients will survive through hospital discharge.