In the present study we investigated the enantioselectivity in the pharmacokinetics of metoprolol administered in a multiple-dose regimen as the racemate. The study was conducted on 10 patients of both sexes with mild to severe essential hypertension, aged 28 to 76 years, with normal hepatic and renal function and phenotyped as extensive metabolizers of debrisoquine (urine debrisoquine to 4-hydroxydebrisoquine ratios of 0.28 to 6.56). The patients were treated with racemic metoprolol (two 100 mg tablets every 24 h) for 7 days. Serial blood samples were collected at times zero, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 22, and 24 h and urine at each 6 h period until 24 h after metoprolol administration. The plasma concentrations of the (-)-(S)- and (+)-(R)-metoprolol enantiomers were determined by HPLC using a chiral stationary phase (Chiralpak AD, 4.6 x 250 mm) and fluorescence detection. The enantiomeric ratios differing from one were evaluated by the paired t test and the results are reported as means (95% CI). No differences were observed between metoprolol enantiomers in half-lives and absorption, distribution and elimination rate constants. However, the following differences (p < 0.05) were observed between the (-)-(S) and (+)-(R) enantiomers: maximum plasma concentration, C(max), 179.99 (123. 33-236.64) versus 151.30 (95.04-207.57) ng/mL; area under the plasma concentration versus time curve, AUC(0-24)(SS), 929.85 (458.02-1401. 70) versus 782.11 (329.80-1234.40) ng h/mL; apparent total clearance, Cl(T)/f, 1.70 (0.79-2.61) versus 2.21 (1.06-3.36) L/h/kg, apparent distribution volume, Vd/f, 10.51 (6.35-14.68) versus 13.80 (6.93-20. 68) L/kg, and renal clearance, Cl(R), 0.06 (0.05-0.08) versus 0.07 (0.05-0.09) L/kg. The enantiomeric ratios AUC((-)-(S))/AUC((+)-(R)) ranged from 1.14 to 1.44, with a mean of 1.29. The data obtained demonstrate enantioselectivity in the kinetic disposition of metoprolol, with plasma accumulation of the pharmacologically more active (-)-(S)-metoprolol enantiomer in hypertensive patients phenotyped as extensive metabolizers of debrisoquine.