The β-adrenoceptor activity of the newly synthesized antagonist bisoprolol ((±)-1-[4-(2-isopropoxy-ethoxymethyl)-phenoxy]-3-isopropylamino-2-propanol, hemifumarate), has been compared with the effect of several reference compounds in anesthetized dogs and guinea pigs. In anesthetized, bivagotomized dogs, isoprenaline dose-response relations for increase in heart rate and decrease in diastolic blood pressure were established. Bisoprolol had the largest β1/β2 ratio, i.e., 147 (102-292). Practolol showed a β1/β2 > 17; betaxolol 6-15; acebutolol, atenolol, and metoprolol 1.1-3.2; mepindolol 0.6-1 and propranolol 0.2. In artificially ventilated guinea pigs, the activity of bisoprolol on histamine-induced increase in tracheal lateral pressure (TLP) and basal heart rate (HR) was tested: using doses taken at TLP (30 mm Hg) and HR (250 beats/min), bisoprolol exhibited the most pronounced ratio TLP/HR of 124 ± 59, followed by atenolol 33 ± 23, metoprolol 25 ± 15, betaxolol 12 ± 4, propranolol 1 ± 0.3, and celiprolol 0.23 ± 0.19. These experiments indicate that bisoprolol possesses a pronounced β1-selectivity, which seems to be superior to that of known β1-selective antagonists.