Plasma concentration and urinary excretion of total and 2 active metabolites of metoprolol have been studied in patients with varying degrees of renal impairment and in healthy subjects after intravenous and oral administration of 20 and 50mg of3H-metoprolol tartrate respectively.Renal clearance of total metabolites correlated directly with51Cr-EDTA clearance (r = 0.95, p < 0.001). A reduction of glomerular filtration rate (GFR) by 70 to 80% increased the elimination half-life of total metabolites and of the active metabolite a-hydroxymetoprolol about 3-fold.Significant accumulation was, however, only observed in the patients with a GFR of about 5ml/min. Even in these patients, the contribution of a-hydroxymetoprolol to the &bgr;-adrenoceptor blocking effect of metoprolol will be negligible. The second active metabolite studied is eliminated via biotransformation, and the urinary excretion as well as the plasma concentration of this metabolite were extremely low in comparison with those of the parent drug.