Background: Congestive heart failure (CHF) is characterized by increased activity of the renin-angiotensin system. Recent experimental studies have shown that infusion of angiotensin II results in depressed plasma levels of insulin-like growth factor 1 (IGF-1) and weight loss. We have previously reported that stable patients with CHF have decreased activity of the growth hormone (GH)-IGF1 axis. We have hypothesized, therefore, that angiotensin- converting enzyme (ACE) inhibition therapy should restore GH-IGF1 activity in CHF patients. Methods and Results: Nine patients with stable CHF who were taking digitalis and diuretics, New York Heart Association functional class III were studied before and after 8 weeks of therapy with Enalapril (10 mg twice daily). We measured IGF1 levels, radionuclide left ventricular ejection fraction (EF) and peak oxygen consumption (PV(O2)). We found that 7 of 9 patients had abnormally low levels of IGF1 (0.2-0.5 mU/ml). IGF1 levels reverted to normal after Enalapril therapy (0.36 ± 0.03 to 0.8 ± 0.14 mU/ml, P = .004). This was associated with a significant increase in EF (27.4 ± 1.1 to 31.4 ± 0.9%) and PV(O2) (14.8 ± 1.2 to 18.6 ± 1.5 ml/kg/min) values (P < .05). Conclusion: Chronic ACE inhibition therapy restored previously reduced IGF1 plasma levels in patients with CHF, most likely by reducing angiotensin II activity.