To study the physiologic role of human myocardial beta-2 adrenoceptors, the beta adrenoceptor subtype(s) involved in the effects of catecholamines in vitro on the force of contraction and in vivo on heart rate were characterized. In vitro on both isolated electrically driven right and left atrial and left papillary muscle preparations, isoprenaline and adrenaline caused positive inotropic effects via beta-1 and beta-2 adrenoceptor stimulation. In the atria both beta-1 and beta-2 adrenoceptor stimulation increased contractile force to a maximum; in left papillary muscle, however, only beta-1 adrenoceptor stimulation maximally increased contractile force, whereas beta-2 adrenoceptor stimulation caused only submaximal increases. Noradrenaline, on the other hand, caused a positive inotropic effect nearly exclusively via atrial and ventricular beta-1 adrenoceptor stimulation. In vivo in 10 healthy volunteers isoprenaline-induced tachycardia was antagonized with equal potency by the beta-2 adrenoceptor-selective antagonist ICI 118,551 and the beta-1 adrenoceptor-selective antagonist bisoprolol indicating that it is mediated by cardiac beta-1 and beta-2 adrenoceptor stimulation to about the same degree. In contrast, exercise-induced tachycardia (that is mediated mainly by noradrenaline released from the neurons) was antagonized only by bisoprolol but not by ICI 118,551. It is concluded that in humans under normal physiologic conditions contractility and/or heart rate is regulated only by cardiac beta-1 adrenoceptors. In situations of stress, however, when large amounts of adrenaline are released from the adrenal medulla, stimulation of cardiac beta-2 adrenoceptors could contribute to additional increases in contractility, heart rate, or both.