OBJECTIVE--To determine whether efferent muscle sympathetic nerve activity diminishes in subjects with dilated cardiomyopathy who improve after long term treatment with metoprolol. METHODS--Microneurographic, echocardiographic, plethysmographic, and neurohumoral data were obtained immediately before and 20 months after the addition of beta blockade in seven subjects with idiopathic dilated cardiomyopathy with clinical deterioration despite conventional treatment. RESULTS--Six subjects (three men, three women, aged 24-62 years) were restudied after a mean (SEM) of 20 (2.4) months treatment with metoprolol (45.8 (2.6) mg/d). Long term treatment was associated with decreases in left ventricular end diastolic and end systolic diameter (P < 0.005), left ventricular mass index (P < 0.05), and atrial natriuretic factor (P < 0.05), and increases in fractional shortening (P < 0.05) and mean blood pressure (P < 0.05). There was a 50% reduction in peroneal muscle sympathetic nerve activity (from 49.2 (10.1) to 24.5 (4.7) bursts/min; (P < 0.005) and a 62% decrease in calf vascular resistance (from 56.2 (4.4) to 21.2 (5.7) units; P < 0.005). This reduction in pulse synchronous nerve activity was not simply a function of bradycardia (heart rate fell from 94.2 (4.6) to 62.8 (5.7) beats/min; P < 0.005) since muscle sympathetic burst incidence also decreased (from 51 (8.7) to 37.5 (5.2) bursts/100 heart beats; P < 0.05). Similar haemodynamic improvement was observed in the seventh subject, who was switched to sotalol 200 mg/d and restudied after 20 months, but burst frequency was 50% higher and calf vascular resistance 93% higher. CONCLUSIONS--Muscle sympathetic nerve activity and calf vascular resistance decrease in patients with dilated cardiomyopathy who improve after long term treatment with metoprolol. Inhibition of central sympathetic outflow may be one mechanism by which metoprolol benefits such subjects.