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SUMMARY Trimethoprim-sulfamethoxazole and parenteral pentamidine isethionate are effective in 60 to 80 per cent of AIDS patients with pneumocystis pneumonia. Adverse reactions are frequent with both agents, but because the adverse reactions are less severe with trimethoprim-sulfamethoxazole, this agent is the drug of choice for patients who are not known to be intolerant of it. The recommended duration of therapy is 21 days. Aerosolized pentamidine and intravenous trimetrexate are investigational agents that show considerable promise, but their role in the therapy of pneumocystis pneumonia will have to be demonstrated in controlled trials. For patients who fail to respond to conventional agents after 5 to 10 days of therapy, therapeutic alternatives to consider would be trimetrexate, DFMO, or high-dose corticosteroids, the latter given with conventional agents. Prophylaxis against pneumocystis pneumonia is appropriate for HIV- infected patients with fewer than 300 T4 lymphocytes per cu mm, even if they are receiving zidovudine (Retrovir). It also should be considered in patients with a prior history of this infection, irrespective of the T4 count. The efficacy of trimethoprim-sulfamethoxazole, pyrimethamine-sulfadoxine, or aerosolized pentamidine has not yet been substantiated. Many patients cannot tolerate the first two combinations chronically.