The efficacy and safety of esmolol, an ultra-short-acting beta-adrenergic blocking agent (elimination half-life, 9 min), was investigated in 358 patients with supraventricular tachyarrhythmias (SVTs) in three multicenter studies (placebo-controlled, propranolol-controlled, and open-label baseline-controlled) and in 19 patients with myocardial ischemia (acute myocardial infarction or unstable angina) in a single-center, open-label study. Esmolol was infused intravenously in doses ranging from 25 micrograms/kg/min to 300 micrograms/kg/min. In SVT studies, efficacy was judged by one or more of the following: a reduction of at least 15% to 20% from the average baseline heart rate, heart rate less than 100 beats/min, or conversion to normal sinus rhythm (NSR). Results revealed that esmolol was superior to placebo and equal to propranolol in controlling heart rate in SVT patients. Conversion to NSR was comparable in patients treated with esmolol (14%) and in those treated with propranolol (16%). The majority of patients achieved therapeutic response at esmolol doses of 200 micrograms/kg/min or less. Among esmolol-treated patients, recovery from beta blockade (i.e., heart rate approaching baseline levels) was achieved within ten minutes after discontinuation of infusion, indicating a brief duration of action of esmolol. In contrast, beta blockade persisted 4.5 hours after discontinuation of propranolol. In patients with myocardial ischemia, esmolol effectively reduced heart rate and blood pressure, thereby decreasing rate-pressure product. The most frequent adverse effect in patients treated with esmolol was hypotension. No clinically significant laboratory abnormalities were reported in esmolol-treated patients. Esmolol was well tolerated in patients infused for durations of up to 24 hours and in patients with conditions for which treatment with beta blockers is inappropriate. These results suggest that esmolol effectively and rapidly controls the heart rate in patients with SVT and in patients with acute myocardial ischemia. Furthermore, because of its short half-life, esmolol offers excellent benefits as compared with the currently available beta-adrenergic blockers in the treatment of critically ill patients. Esmolol was well tolerated by patients for whom beta blockers in general would be unsuitable.