Debrisoquine (DQ) has no chiral centre, but hydroxylation in position 4 leads to formation of an asymmetric carbon centre with two possible enantiomers, their absolute configuration being R(-) and S(+)-4-hydroxydebrisoquine (4-OHDQ). Since the absolute stereochemistry of the 4-hydroxylation of DQ in man is unknown, the enantioselectivity of this process was studied in panels of extensive (EM) and poor metabolizers (PM) of DQ. In EM subjects 4-hydroxylation of DQ leads almost exclusively to the formation of S(+)-4-OHDQ. In contrast, PM subjects were not only characterized by a decreased total 4-OHDQ formation but also a marked loss of enantioselectivity in product formation. Between 5 to 36% of total 4-OHDQ was excreted as R(-)-4-OHDQ.