We determined the relationship between theβ1- andβ2-adrenergic receptor subtypes in isolated myocytes and their physiological responsiveness in chronically instrumented conscious baboons and rats. In conscious baboons, isoproterenol (ISO) (0.02μg/kg) increased left ventricular (LV) dP/dtby 89±6.7% from 2898±370 mmHg/s and only by 13±3.3% from 2491±146 mmHg/s afterβ1-adrenergic receptor blockade, indicating that the predominant physiological response was mediated byβ1-adrenergic receptors. Decreases in mean arterial pressure (−11±0.5 mmHgv−16±4.6 mmHg) and coronary vascular resistance (−3.1±0.4v−3.6±0.4 mmHg/ml/min) induced by ISO were not different before and afterβ1-blockade, indicating thatβ2-adrenergic receptors were not blocked. In conscious rats, ISO (0.4μg/kg) increased LV dP/dtby 50±4.9% from 13 252±2002 mmHg/s and only by 10±3.9% from 10 793±1364 mmHg/s afterβ1-adrenergic receptor blockade; whereas decreases in mean arterial pressure induced by ISO were not different before and afterβ1blockade (−19±2.4 mmHgv−16±2.2 mmHg), i.e. very consistent with the physiological responses in baboons.In vitrostudies of isolated myocytes, using radioligand binding with125I-cyanopindolol (125I-cyp) and the subtypeβ1-selective antagonist betaxolol and theβ2-selective antagonist ICI 118 551 indicated that theβ1/β2ratio of rat myocytes was 92/8; whereas baboon myocytes were more equally distributed (59/41). Thus, in both species the preponderance of effects of ISO on ventricular function wasβ1-adrenergic receptor mediated, which is consistent with theβ1/β2ratio in rat myocytes but not in baboon myocytes, where a significant fraction ofβ2-adrenergic receptors does not appear to exert an effect on conctractilityin vivo.