The pediatric myocardium has been shown to thicken markedly during steroid administration for the treatment of pulmonary or neurologic disease. Yet, in the pediatric heart transplant patient, left ventricular (LV) thickening is sometimes used as a marker for rejection without accounting for steroid immunosuppression. The aim of this study was to determine timing and correlates of changes in LV thickness in pediatric cardiac transplant patients. In 11 patients (11 days old to 16 years old), LV thickness (mass) was first measured during the entire post-transplant course. Second, thickness was measured before and during rejection. Last, to separate the independent effects of rejection and steroids on LV mass, echocardiograms were reviewed in the immediate post-transplant period, when our protocol prescribes dramatic changes in steroid doses and rejection episodes were rare. Specifically, the donor heart underwent 5 evaluations: at donation, at peak steroid dose, 5 days after peak steroid dose, at moderate steroid dose, and at very low maintenance dose. LV mass changed most dramatically and consistently during the first 20 to 40 days after transplant. Thereafter, mass had little consistent changes and did not change significantly during any of the 52 rejection episodes. Mass increased 5 days after peak steroid dose (54 +/- 30 to 74 +/- 38 g/ht2.7, p < 0.05) and decreased during low maintenance levels of steroids. Thickening was associated with cumulative steroid dose (r = 0.66, p = 0.03) and age (r = -0.62, p = 0.04). Thus, in pediatric heart transplant patients, as in other pediatric diseases, LV thickening is associated with steroid administration. Thickening may be an unreliable marker for acute cellular rejection.