The properties of the newly developed selective beta 1-adrenoceptor antagonist bisoprolol (EMD 33152) were investigated by in vitro and in vivo studies. Binding studies with (-)-[125I] iodocyanopindolol (ICYP) revealed that the affinity of (+/-)-bisoprolol to beta 1-adrenoceptors was approximately 100 times higher than to beta 2-adrenoceptors. This high beta 1-adrenoceptor selectivity of bisoprolol could be confirmed in binding studies with the tritiated compound (-)[3H] bisoprolol, which labelled in rabbit lung membranes--a tissue known to contain 80% beta 1- and 20% beta 2-adrenoceptors--exclusively beta 1-adrenoceptors. In physiological studies, (+/-)-bisoprolol was found to be devoid of any intrinsic sympathomimetic activity (ISA), since it had no positive chronotropic effects on spontaneously beating right atria of reserpinized rats. On isolated electrically driven human right atria, (+/-)-bisoprolol was approximately 30 times more potent in antagonizing the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline (pA2-value, 8.42) than the beta 2-adrenoceptor-mediated positive inotropic effect of procaterol (pA2-value, 6.99). To test the beta 1-adrenoceptor selectivity in vivo, the effects of bisoprolol administration (1 X 10 mg/day for 9 days) on lymphocyte beta 2-adrenoceptor density [assessed by (-)-ICYP binding] in healthy volunteers were compared with those of the nonselective beta-adrenoceptor antagonists propranolol (4 X 40 mg/day for 9 days) without ISA, and pindolol (2 X 5 mg/day for 9 days) with ISA.(ABSTRACT TRUNCATED AT 250 WORDS)