The original Lands classification considered cardiac beta-adrenoceptors to be predominantly beta 1 in type and to respond to both noradrenaline and adrenaline. Radioligand binding studies subsequently identified substantial numbers of beta 2-adrenoceptors in cardiac tissue. Studies in man employing intensive exercise, isoprenaline testing and a variety of selective and non-selective beta-adrenoceptor antagonists would now suggest that under certain circumstances these receptors may be functionally active. Severe exercise, as a sympathetic stimulus, is associated with high circulating noradrenaline concentrations, and appears to produce tachycardia predominantly by cardiac beta 1-adrenoceptor activity. In contrast, isoprenaline testing increases heart rate by a number of mechanisms: it stimulates beta 1-adrenoceptor activity in the sinoatrial node; it may result in reflex vagal withdrawal; and it appears to stimulate cardiac beta 2-adrenoceptors directly. In addition, isoprenaline also facilitates noradrenaline release by presynaptic beta 2-adrenoceptors. Thus the effects of isoprenaline would appear to mimic stress in man with the subsequent release of adrenaline from the adrenal medulla and its complex interaction directly and indirectly with both cardiac beta 1 and beta 2-adrenoceptors. These differing circumstances may also influence the relative efficacy of beta 1-selective and non-selective beta-adrenoceptor agonists and antagonists.