We evaluated the incidence of prophylaxis failure with aerosolized pentamidine (AP) for Pneumocystis carinii pneumonia (PCP) in Japanese patients with human immunodeficiency virus (HIV) infection, and we examined the short- and long-term effects of AP on pulmonary function. The patients inhaled 300 mg of pentamidine by ultrasonic nebulizer, after the inhalation of procaterol (80 micrograms), every 4 weeks. PCP developed in 2 of 16 patients receiving primary prophylaxis with AP, and in 4 of 13 patients with secondary prophylaxis. The CD4(+) T-lymphocyte count was very low in the patients with prophylaxis failure. The chest radiographic presentations were atypical in 4 of the 6 patients with prophylaxis failure. There were no significant changes in the vital capacity (VC), VC/predictive VC (%VC), forced expiratory volume in 1 s (FEV(1.0)), FEV(1.0)/forced vital capacity (FEV(1.0)%), and maximum expiratory flow rate at 25% of vital capacity (MEF(25))/height comparing values before and after initial AP treatment. However, a reduction of oxygen saturation (SpO(2)) of over 3% was noted in 4 patients during the initial AP administration. In 9 patients receiving AP prophylaxis for more than 36 months, we compared the pulmonary function parameters between the baseline and final observations (mean, 52.7 months). There were no changes in VC, %VC, FEV(1.0,) FEV(1.0)%, and SpO(2), but there was a statistically significant decline in MEF(25)/height after long-term AP treatment. We concluded that the incidence of prophylaxis failure with AP for PCP in Japanese patients was similar to that in Western patients, and that long-term AP treatment affected MEF(25)/height in spite of the safe pulmonary effects in short-term AP inhalation.