Among 630 patients with human immunodeficiency virus infection, 70 patients with new-onset seizures were studied. Generalized seizures occurred in 66 patients (94%): they occurred as the initial seizure in 56 patients (80%) and during follow-up in another 10 patients (14%). Partial seizures (18 patients), status epilepticus (10 patients), and recurrent seizures (38 patients) were also noted. Identified processes included cerebral toxoplasmosis in 11 patients, cerebral lymphoma in 8, metabolic derangement in 8, cryptococcal meningitis in 7, and vascular infarction in 4. In 32 patients (46%) seizures were not associated with identifiable brain lesions and were believed to result from human immunodeficiency virus cerebral infection. Phenytoin treatment was associated with adverse drug reactions in 16 of 62 patients who received it. Our results suggest that the majority of patients with human immunodeficiency virus and seizures do not have secondary focal brain lesions as the cause of the seizures and that human immunodeficiency virus infection alone can, and often does, cause seizures.