To determine the respiratory effects on health care workers of occupational exposure to aerosolized pentamidine (AP) used for the prophylaxis of Pneumocystis carinii pneumonia, we designed a clinical prospective study using subjects as their own controls. Sixteen health care workers whose job duties included administration of AP at one or more of nine San Francisco Bay Area medical centers participated in the study. Pentamidine concentrations ranged in breathing zone samples from < 0.03 to 62.2 micrograms/m3. Pentamidine was not detected in the urine of any of the subjects. There were no significant increases in symptoms on days when AP was administered. Cross-workshift spirometry on days when AP was administered showed a statistically significant mean decrease (0.14 liter) in forced expiratory volume in 1 second. There was no statistically significant difference in mean diurnal variation of peak expiratory flow rate on days when AP was administered. Methacholine inhalation challenge testing did not show a statistically significant mean change in airway responsiveness across the workweek. The ambient concentrations of pentamidine that we measured document that detectable occupational exposure to AP can occur in poorly ventilated treatment rooms. The cross-workshift decrement in forced expiratory volume in 1 second that we observed in association with AP administration supports the respiratory tract irritant potential of inhaled pentamidine. We recommend that steps be taken to minimize health care worker exposure to AP.