Toxoplasmic encephalitis has been recognized as a major CNS complication in patients with AIDS and is the most frequent cause of focal intracerebral lesions in these patients. This complication of AIDS is almost always observed in patients who have a chronic (latent) infection with Toxoplasma gondii. Therefore, patients who from the outset of their HIV infection or AIDS are known to have antibodies to T. gondii should be considered at risk for development of toxoplasmic encephalitis. Although serologic tests cannot distinguish active from latent infection, a patient who is seronegative for Toxoplasma antibodies is unlikely to have toxoplasmic encephalitis. Neuroradiologic studies may be highly suggestive of toxoplasmic encephalitis, but, at present, the definitive diagnosis can be made only by demonstration of Toxoplasma in brain tissue. The unique pathogenesis of toxoplasmic encephalitis in patients with AIDS makes intensive primary therapy followed by a lifelong suppressive regimen necessary. We recommend 6 weeks of high doses of pyrimethamine and sulfadiazine (or trisulfapyrimidines) as primary therapy for the acute disease followed by daily administration of reduced doses of these drugs. The use of clindamycin as an alternative drug for primary therapy, at least at present, must be regarded as investigational and should be reserved for patients who suffer severe reactions to the sulfonamides. As most patients will respond to their primary therapy, those who fail to improve clinically and radiologically to therapy within 10 days should be evaluated for additional or alternative causes of their intracerebral pathology. This will often necessitate brain biopsy.