We retrospectively compared the clinical manifestations, laboratory features, and outcome of cryptococcal meningitis in 44 human immunodeficiency virus (HIV)-positive and 21 HIV-negative patients in Durban, South Africa, and contrasted our findings with those in the developed world. Cryptococcal meningitis was the initial AIDS-defining illness in 84% of patients. Headache, fever, convulsions, neck stiffness, and neurological signs were more common in HIV-positive patients. We detected neurological abnormalities in 50% of the HIV-positive group. Seventeen percent of HIV-positive patients had completely normal CSF indices. HIV-positive patients with cryptococcal meningitis frequently had oral candidiasis and tuberculosis as coexistent illnesses. Prognostic factors identified in the West do not appear to be applicable in Africa. Death during hospitalization was significantly higher in the HIV-positive group. HIV-associated cryptococcal meningitis in Africa is apparently associated with higher rates of neurological complications and death than is such disease in developed countries of the world.