We evaluated 43 AIDS patients on prophylaxis with aerosol pentamidine (60 mg biweekly) after Pneumocystis carinii pneumonia (PCP). The effects of patients' inhalation compliance and of laboratory data during the initial PCP on subsequent PCP relapses were assessed. After a median of 8 months (range, 2-21.5 months) on pentamidine prophylaxis, 13 patients suffered a PCP relapse. Six of them had missed at least one inhalation within the last month before the relapse. Two of these six relapses were fatal. The relapse occurrence was significantly associated with the percentage of missed inhalations. Additional significant associations were found between relapses, low levels of T4 lymphocytes, and elevated serum lactate dehydrogenase during the initial PCP episode (29 patients). Mean levels of T4 lymphocytes were 27/mm3 and 47/mm3 in patients with and without subsequent relapses, mean levels of lactate dehydrogenase were 692 U/L and 605 U/L, respectively. Multivariate Cox regression did not reveal further differences between patients with and without relapses. The increased relapse risk associated with poor inhalation compliance stresses the need for appropriate guidance and motivation of the patients.