We compared the change in passive respiratory system compliance (Crs) and resistance (Rrs) after albuterol aerosol treatment administered by either low-flow nebulizer (NEB) or a metered dose inhaler (MDI) and spacer into a ventilator circuit. We hypothesized that albuterol delivered to ventilated infants older than 7 days of life by an MDI and a spacer would improve Crs more than albuterol delivered by a low-flow nebulizer. The treatments were administered 6 hr apart to premature infants with Crs < or = 0.8 mL/cm H2O per kg, requiring ventilation after 7 days of age. Patients served as their own controls and treatment order was randomized. Eighteen studies were performed in eight infants before and 1 and 3 hr after treatment. Differences between methods were compared by analyses of variance. Mean (range) birth weight and study age were 888 (619-1,283) g and 12 (7-29) days, respectively. Mean respiratory system compliance increased by 34% with MDI and by 11% with NEB at 1 hr after treatment (P < 0.02). By 3 hr after treatment, Crs returned to baseline with both methods of aerosol delivery. There was no significant difference in Rrs between the two methods at 1 and 3 hr after treatment. We conclude that albuterol delivered by MDI improves Crs more than low-flow NEB in ventilated premature infants.