To demonstrate the presence of functional cardiac β2-adrenoceptors in man, we studied the responses to intracoronary injections of salbutamol in three groups of six patients. We injected salbutamol, a selective β2-adrenoceptor agonist, into the right coronary artery to avoid peripheral vasodilator action and to stimulate the sinoatrial node directly. Salbutamol injections caused a sinus tachycardia. The same doses of salbutamol injected into the aortic root caused no change in heart rate, ruling out a systemic effect. The mean dose required to cause an increase in heart rate of 30 beats/min (IHR30) was 2.6 μg in the first group of six patients. In 12 other patients salbutamol was given after β-blockade to confirm the β2-selectivity of the responses. Doses of practolol (β1,-selective blockade) and of propranolol (β1- and β2-blockade) that had equal β1-blocking activity were used. In six patients who were given practolol, the mean IHR30dose was 2.1 μg. In six patients who were given propranolol, the mean IHR30dose was significantly greater at 64 μg (p<0.001, practolol vs. propranolol). This study demonstrates that direct cardiac β2-adrenoceptor stimulation in man has a positive chronotropic effect.