Varying results have been reported on the association of beta-adrenergic receptor polymorphisms with blood pressure (BP) response to beta-blockers. We investigated the influence of ADRB1 Ser49Gly and Arg389Gly, and ADRB2 Gly16Arg and Glu27Gln polymorphisms on ambulatory BP response to bisoprolol and three other antihypertensive drug monotherapies in a placebo-controlled, double-blind, cross-over study with 233 moderately hypertensive men. ADRB1 Ser49Ser homozygotes tended to have a better ambulatory BP response to bisoprolol but the difference was statistically nonsignificant. ADRB1 Arg389Arg homozygotes did not show better BP response to bisoprolol than the other genotypes. There were no significant associations of ADRB2 polymorphisms with BP responses to any of the study drugs. The results from this controlled study in hypertensive men do not support clinical use of common polymorphisms in ADRB1 and ADRB2 in predicting BP responses to beta-blockers or to three other antihypertensive drugs.