The efficacy and toxicity of aerosolized pentamidine was evaluated in 78 AIDS patients given 60 mg biweekly as secondary prophylaxis against Pneumocystis carinii pneumonia (PCP). Patients were monitored for clinical progression and mortality and were compared to 42 historical controls given 200-300 mg i.v. pentamidine biweekly. The relapse rates did not differ markedly between the two groups, and the PCP-free rates in survivors were at 12 months 0.83 and 0.77, respectively. Seventy-one new AIDS-defining events and 25 deaths were recorded in patients on aerosolized pentamidine compared to 29 AIDS events and two deaths in patients on intravenous pentamidine. Recurrent PCP contributed to death in only one case of the aerosolized pentamidine group. PCP is not a serious clinical problem in immunodeficient patients taking pentamidine prophylaxis by either route compared to the progression of clinical HIV disease and death.