The effects of selective beta 1- as compared to nonselective beta-adrenergic blocking drugs on the peripheral circulation have not been adequately investigated. Ten healthy subjects received placebo for 1 wk followed by 4 wk of either propranolol or metoprolol in equivalent but increasing doses each week. Subjects then crossed over to the other sequence of placebo and drug. Measurements of calf blood flow, mean blood pressure, and calculation of calf vascular resistance were obtained at rest, after three loads of supine exercise on a bicycle ergometer, and during isoproterenol infusion testing. At the doses chosen, both beta-adrenergic blocking drugs induced equivalent decreases in exercise heart rate. Metoprolol lowered resting and exercise mean blood pressure at most doses, whereas propranolol had less of an effect on this variable. Neither drug altered resting or exercise calf blood flow or vascular resistance. More isoproterenol was required to increase the heart rate and decrease the vascular resistance during treatment with propranolol than with metoprolol. We conclude that in normotensive subjects metoprolol is somewhat more effective than propranolol in lowering mean arterial pressure during exercise when the drugs are given at doses equivalent in effects on exercise heart rate. Neither drug has a deleterious effect on calf blood flow or vascular resistance. Despite this, a marked separation between the vascular beta 2-adrenergic-blocking effects of these drugs can be demonstrated with an isoproterenol infusion indicating beta 2-adrenergic-receptor sparing by metoprolol.