Three patients with acquired immune deficiency syndrome (AIDS), central nervous system toxoplasmosis, and hypersensitivity to sulfadiazine were given treatment with clindamycin plus pyrimethamine. All three showed improvement clinically with resolution of symptoms. Two patients had computed tomographic evidence of improvement with reduction in size or clearing of cerebral lesions and the third had resolution of chorioretinitis. Another patient who had a relapse during administration of standard therapy (pyrimethamine plus sulfadiazine) had a clinical response when clindamycin was added to this regimen. Clindamycin in combination with pyrimethamine, or as an adjunct to standard therapy, may be useful in the treatment of central nervous system toxoplasmosis in patients with AIDS.