We reviewed 2,107 consecutive autopsies with neuropathologic examination at the Medical Center Hospital of Vermont, and identified 92 cases with significant pathologic evidence for infection involving the central nervous system (CNS). Of these, 35 took the form of multiple microabscesses. There were 19 men and 16 women, mean age 56. All patients were chronically ill, usually with an associated impaired immunity. The lung was the most frequent site of primary infection, and sepsis was often present. The most commonly identified causative organisms were Staphylococcus aureus and Candida albicans. Patients with CNS microabscesses developed a progressive encephalopathy associated with waxing and waning signs and symptoms. Laboratory and neuroradiologic studies were not helpful in elucidating the problem. We conclude that multiple microabscesses are a frequent, usually unrecognized, manifestation of CNS infection, and should be considered in the differential diagnosis of encephalopathy in hospitalized patients with chronic disease, immunosuppression and sepsis.