Aerosolized pentamidine is widely used in adult patients with human immunodeficiency virus as both prophylaxis and therapy forPneumocystis cariniipneumonia. The aim of this study was to evaluate the safety of a monthly regimen of aerosolized pentamidine in human immunodeficiency virus-infected infants. Seven human immunodeficiency virus-infected infants, ages 3.5 to 11 months, were given a total of 45 monthly treatments of aerosolized pentamidine. The infant's dose of pentamidine was based on an adult dosage of 300 to 600 mg/month, adjusted for minute ventilation and weight. There were no discernible clinical side effects in 62% (28 of 45) of the treatments. Observed toxicity included mild to moderate coughing, mild wheeze and transient arterial desaturation as measured by pulse oximetry. Pulmonary function data revealed an increased tidal volume (P< 0.005) and an increased pulmonary resistance (P< 0.02) post-pentamidine treatment. Urinary pentamidine concentrations were obtained and pentamidine was detected in all tested samples suggesting pulmonary deposition and systemic absorption. In conclusion aerosolized pentamidine appears to be a relatively safe, well-tolerated treatment in infants, with side effects similar to those seen in adults.