Clinical trials have shown dexamethasone's beneficial effects on the pulmonary status of infants with bronchopulmonary dysplasia; however, hypertrophic cardiomyopathy has been a reported complication of this therapy with no known mechanism. Our study was designed to test the hypothesis that therapeutic dexamethasone doses would induce myocardial hypertrophy. Newborn Sprague-Dawley rats were randomly assigned to receive dexamethasone 0.125 mg/kg/day, while paired littermate controls received saline placebo. The daily body weights were recorded and pups were sacrificed after 5 or 7 days of treatment. The heart weight to body weight ratio was used as a gross index of myocardial mass. Myocardial protein content, total protein to total DNA ratio, actin content and myosin heavy chain content were used as biochemical indices of hypertrophy. Our results included an increased heart weight to body weight ratio with elevation of the total protein content, actin content and total protein to total DNA ratio after both 5 and 7 days. We conclude that dexamethasone induces myocardial hypertrophy in neonatal rats.