The contribution of debrisoquine polymorphism to the metabolism and action of beta-adrenoceptor antagonists (beta-blockers) varies widely between drugs. Oxidation phenotype is a major determinant of the metabolism, pharmacokinetics and some of the pharmacological actions of metoprolol, bufuralol and timolol. The poor metabolizer phenotype is associated with an increased area under the plasma drug concentration vs. time curve, a prolongation of elimination half-life and a more intense and sustained beta-blockade. The stereoselective metabolism of metoprolol also displays phenotypic differences, which should be taken into account when interpreting plasma concentration vs. response relationships. Studies in vivo and in vitro have identified some of the metabolic pathways which are subject to this defect, namely the alpha-hydroxylation and the O-demethylation of metoprolol and the 1'-hydroxylation of bufuralol. In contrast, the pharmacokinetics and pharmacodynamics of propranolol, which is also extensively oxidized, are not related to debrisoquine polymorphism, although 4'-hydroxypropranolol formation is deficient in the poor metabolizer phenotype. The disposition of atenolol, which is almost completely eliminated unchanged by renal and faecal excretion, is independent of oxidation phenotype. If standard doses of some beta-blockers are used in poor metabolizers, these patients may be susceptible to concentration-related adverse reactions and they may also require lower and less frequent dosing for control of angina pectoris.