To assess the efficacy and safety of the ultra short-acting beta-blocking agent, esmolol, in acute unstable angina, we administered esmolol to 21 patients who had persistent angina despite conventional medical therapy. Following a baseline Doppler echocardiographic examination, esmolol was titrated to reduce the rate-pressure product by at least 20%. Once the patients had been receiving a maintenance dosage for 30 minutes, Doppler echocardiographic studies were repeated. Mean esmolol dose at target response was 17 +/- 16 mg/min, with the dosage range of 8 to 24 mg/min. Esmolol was effective in alleviating anginal chest pain in 18 of the 21 patients. Seven patients eventually underwent percutaneous transluminal coronary angioplasty (PTCA) and eight had coronary bypass surgery. The remainder were discharged receiving medical therapy including oral beta-blockade. During esmolol therapy, heart rate and blood pressure decreased significantly (86 +/- 14 to 68 +/- 12 beats/min and 125 +/- 16 to 103 +/- 20 mm Hg, both p < 0.001). Cardiac output decreased from 5.4 +/- 1.3 to 4.5 +/- 1.1 L/min (p < 0.001) secondary to a decrease in heart rate as stroke volume remained unchanged. Left ventricular ejection fraction increased from 47 +/- 12 to 49 +/- 13 with esmolol therapy, although this change was not statistically significant. Both the one third filling fraction as well as E/A ratio (ratio of early-to-late diastolic filling velocities) increased with esmolol therapy (35 +/- 8% to 38 +/- 8% and 0.73 +/- 0.2 to 0.85 +/- 0.23, both p < 0.005), indicating improvement in left ventricular diastolic function. Other than transient hypotension, which quickly resolved upon downward titration of the infusion, there were no significant side effects related to the administration of esmolol. Thus the use of ultra short-acting beta-blockade as add-on therapy in patients with acute unstable angina appears to be both safe and effective. It should be considered early as a treatment option in these patients.