Treatment of chronic lung disease of prematurity requires effective aerosol delivery of different therapeutic agents. Aerosols can be generated by a metered dose inhaler (MDI) or a jet nebulizer. An MDI combined with a spacer device is easier to use and avoids undesirable effects noted in conjunction with jet nebulization. We compared the clinical effectiveness of 200 micrograms (2 puffs) salbutamol delivered from an MDI in conjunction with a valved spacer device (Aerochamber), and 600 micrograms given via jet nebulizer (PariBaby) on 2 consecutive days, the order being randomized. Thirteen spontaneously breathing very preterm infants [mean (SD) gestational age 27.2 (1.8) weeks; birth weight 0.90 (0.34) kg] were studied at a corrected age of 37 (2.3) weeks. Mean (SD) study weight was 1.83 (0.38) kg. Dynamic lung compliance and resistance were determined from measurements of flows, volumes, and transpulmonary pressures, using a pneumotachometer and a small esophageal microtransducer catheter before and 20 min after salbutamol application. Baseline values before salbutamol administration were similar on both occasions: the mean (SD) compliance was 7.7 (3.0) mL.kPa-1.kg-1 pre-MDI plus-spacer and 8.4 (3.1) pre-jet nebulizer; the resistance was 10.4 (4.0) kPa.L-1.s pre-MDI plus-spacer and 9.7 (3.4) pre-jet nebulizer. Following salbutamol, compliance did not change significantly with either MDI plus spacer or jet nebulizer. Resistance fall significantly with MDI plus spacer (mean -2.2; 99.9% CI -0.35, -4.35) and jet nebulizer (-2.4; 99% CI -0.39, -4.42). We conclude that even in small preterm infants 200 micrograms salbutamol via MDI plus spacer improves dynamic resistance as effectively as 600 micrograms via jet nebulizer and may therefore be a preferable mode of aarosol administration.