We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the beta(2)-adrenoceptors. From 216 preselected volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg(16) and Gln(27) (Arg(16)/Gln(27), n = 34), Gly(16) and Gln(27) (Gly(16)/Gln(27), n = 20), and Gly(16) and Glu(27) (Gly(16)/Glu(27), n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly(16)/Glu(27) group than in Gly(16)/Gln(27) and Arg(16)/Gln(27) groups (1.79 +/- 0.66 vs. 0.70 +/- 0.11 and 0.58 +/- 0.12 units, P = 0.03). Similar results were found during exercise (0.80 +/- 0.25 vs. 0.28 +/- 0.08 and 0.31 +/- 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly(16)/Glu(27) (n = 6) and Arg(16)/Gln(27) (n = 7) groups during mental stress (0.33 +/- 0.20 vs. 0.46 +/- 0.21 units, P = 0.50) and exercise (0.08 +/- 0.06 vs. 0.03 +/- 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg(16)/Gln(27) and Gly(16)/Glu(27) groups was similar. In conclusion, women who are homozygous for Gly(16)/Glu(27) of the beta(2)-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.