The frequency, presentation, diagnosis and clinical course of Pneumocystis carinii infections (PCI) were studied during aerosolized pentamidine prophylaxis (AP) and its impact on the spectrum of AIDS-related and other pulmonary infections in HIV-infected hemophiliacs. We conducted an open study on primary (PP) and secondary (SP) AP. Breakthrough P. carinii infections (BPCI) and other infectious complications were analyzed retrospectively. Hemophiliacs without prior P. carinii pneumonia (PCP) who had been reluctant to any prophylaxis and who developed PCP served as control group. Statistical analysis of the efficacy of prophylaxis was performed by calculating confidence intervals of binomial p. Of 73 hemophiliacs (56 on PP and 17 on SP) 10 developed BPCI (7 in PP and 3 in SP) during a mean observation time of 14.9 months (range 0.5-30); total 13.6% (6.7%; 23.7%), PP 12.5% (5.1%; 24%), SP 17.6% (3.7%; 43.4%), confidence intervals at a level of 95%. Three BPCI presented atypically with cavitation (1), pneumothorax (2), Pneumocystis pleuritis (1), dissemination (2) as compared to none in the control group. Sensitivity of bronchoalveolar lavage (BAL) was 88.9%, specificity 100% (both 100% in the control group). PCP was the leading AIDS manifestation (21.3%), CNS manifestations taken together were more frequent (36.2%). Bacterial pneumonia was the most frequent respiratory infection. One patient of the study group with recurrent pneumothorax possibly died of BPCI as compared to no BPCI-related deaths in the control group. Efficacy of prophylaxis in hemophiliacs was comparable to other risk groups. AP alone may be insufficient for the control of PCI in patients with long-term profound immunodeficiency, especially in SP. 30% of BPCI presented atypically.(ABSTRACT TRUNCATED AT 250 WORDS)