Central nervous system (CNS) toxoplasmosis is an important infectious complication of AIDS which requires prolonged treatment. Most cases occur in patients with serologic evidence of prior exposure and therefore appear to result from reactivation of a previously acquired infection. Antibody to Toxoplasma gondii was found in 130 out of 411 patients with AIDS (32%). Of these, CNS toxoplasmosis developed in 31 (24%). By survival analysis, the estimated probability of ever developing CNS infection in antibody-positive individuals was 28%, occurring in 26% of patients within 2 years of the onset of AIDS. All patients with HIV infection should be tested for antibody to T. gondii and monitored for any neurologic change. Methods of prophylaxis for CNS toxoplasmosis in these high-risk patients need to be developed.