In patients with AIDS, toxoplasmosis is the most common cause of CNS mass lesions. Diagnosis is made on the basis of clinical presentation and CAT scan findings and confirmed by demonstration of tachyzoites and/or cysts in tissues obtained by needle aspiration or brain biopsy. Response to therapy with pyrimethamine and sulphadiazine is usually prompt but therapy has to be continued for the lifetime of AIDS patients with CNS toxoplasmosis. To date, no alternative regimens of single or combination drugs appear to be effective in patients who fail, or are unable to tolerate pyrimethamine and sulphadiazine therapy. Relapse rate is high. Clearly, there is a need to organize prospective controlled studies to assess the role of agents such as clindamycin, trimetrexate and other drugs in the treatment of CNS toxoplasmosis in patients with AIDS.