To differentiate beta 1- and beta 2-adrenoceptor-mediated effects in humans, we studied the effects of a 2-wk treatment of 12 male volunteers with the selective beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg/day) and the beta 2-selective antagonist ICI 118,551 (3 x 25 mg/day) on lymphocyte beta 2-adrenoceptor density and responsiveness [10 microM l-isoproterenol (IPN) evoked adenosine 3',5'-cyclic monophosphate (cAMP) increase] as well as on exercise- and IPN-induced changes in lymphocyte beta 2-adrenoceptor density, blood pressure, heart rate, and plasma norepinephrine levels. ICI 118,551 administration increased lymphocyte beta 2-adrenoceptor density and responsiveness by approximately 50%, whereas bisoprolol had no effect. Dynamic exercise on a bicycle and infusion of graded doses of IPN led to an approximately 100% increase in lymphocyte beta 2-adrenoceptor density; this was abolished by ICI 118,551 but not affected by bisoprolol. ICI 118,551 markedly attenuated IPN-induced decrease in diastolic blood pressure but did not affect increase in systolic blood pressure, whereas bisoprolol had opposite effects. The IPN-induced increase in heart rate, however, was antagonized by both bisoprolol and (to a greater extent) ICI 118,551. Finally, ICI 118,551 completely abolished the IPN-induced increase in plasma norepinephrine levels, whereas bisoprolol had no effect. These results indicate that bisoprolol and ICI 118,551 are suitable tools to differentiate in humans beta 1- and beta 2-adrenoceptor-mediated effects.