To assess whether long-term dexamethasone therapy for chronic lung disease (CLD) in infancy is associated with any deleterious cardiac structural effects, we conducted a retrospective review of all preterm infants with CLD born between October 1, 1989, and October 1, 1990, who had serial echocardiographic data available. These infants were divided into three groups based on the length of their exposure to dexamethasone. Group 1 contained nine infants with CLD who did not receive dexamethasone. Group 2 was comprised of six infants who received dexamethasone for less than 8 days. Group 3 contained one infant who received a 26-day course, and 13 infants who received at least one 42-day course of dexamethasone for CLD. Left ventricular hypertrophy was noted in 8 of 14 (57%) infants in group 3; hypertrophy usually was noted near the end of the treatment course. Five of these eight affected infants died; the hypertrophic cardiomyopathy was considered to have contributed to mortality in three of these five infants. Regression of the hypertrophy was noted in the three surviving infants in group 3 after the dexamethasone course was completed. We speculate that prolonged dexamethasone treatment for CLD is associated with hypertrophic cardiomyopathy in a significant portion of preterm infants.