Pulmonary mechanics were measured in 43 preterm neonates (mean +/- SD values of birth weight 1.2 +/- 0.3 kg, gestational age 30 +/- 2 weeks) with respiratory failure who were concurrently randomly assigned to receive conventional mechanical ventilation (n = 22) or high-frequency ventilation (n = 21). The incidence of bronchopulmonary dysplasia was comparable in the two groups (high-frequency ventilation 57%, conventional ventilation 50%). Pulmonary functions were determined at 0.5, 1.0, 2.0, and 4.0 weeks postnatal ages. Data were collected while subjects were in a nonsedated state during spontaneous breathing. These sequential data show similar patterns of change in pulmonary mechanics during high-frequency ventilation and conventional mechanical ventilation irrespective of gestational age, birth weight stratification, or bronchopulmonary dysplasia. There was no significant difference in the pulmonary functions with either mode of ventilation during the acute phase (less than or equal to 4 weeks) of respiratory disease. When evaluated by the clinical diagnosis of bronchopulmonary dysplasia, the pulmonary data suggested a less severe dysfunction in the high-frequency oscillatory ventilation-treated bronchopulmonary dysplasia group compared with the conventional mechanical ventilation-treated group. These results indicate that high-frequency oscillatory ventilation in preterm neonates does not reduce the risk of acute lung injury; however, the magnitude of the pulmonary dysfunction in the first 2 weeks of life merits a reevaluation.