We treated rats with dexamethasone (DEX, 1 mg·kg-1·day-1) and examined the effects of this glucocorticoid on heart protein metabolism using atrial explant and Langendorff perfusion preparations. Fasted rats treated with DEX for 2 days had significantly lower body weights (92% of control, P < 0.001) and larger hearts (106% of control, P < 0.005) than fasted control animals. Protein and RNA concentrations remained constant. In atrial explants, DEX treatment produced a 19% increase in protein synthesis (P < 0.001) and a 13% increase in protein degradation (P < 0.002). In Langendorff-perfused hearts, DEX treatment caused a 36% increase in protein synthesis (P < 0.02), while protein degradation was 8% above control (P > 0.05). Thus, in contrast to their catabolic effects on skeletal muscle, glucocorticoids are anabolic on the heart. The increased accumulation of total cardiac protein during early glucocorticoid administration is mediated entirely via increased rates of synthesis.