Angiotensin-converting enzyme inhibitors have been shown to increase maximal muscle blood flow in parallel to peak VO2 in patients with congestive heart failure (CHF). Whether this increase shifts factors limiting peak aerobic capacity from periphery (skeletal muscle or vessels) to central factors (cardiac or respiratory) is unknown. Comparison of peak oxygen consumption (VO2) obtained during leg cycling (VO2 leg) with peak VO2 obtained during combined leg cycling and arm cranking (VO2 arm + leg) allows determination of the relative role of central or peripheral factors. We compared VO2 leg with VO2 arm + leg before and after 3 months of therapy with quinapril 40 mg in 16 patients with CHF (age 53 +/- 13 years) due to left ventricular systolic dysfunction (ejection fraction 0.25 +/- 0.07). Before quinapril, VO2 arm + leg was significantly higher than VO2 leg (19.0 +/- 3.3 vs 16.9 +/- 3.8 ml/kg/min, p < 0.001), whereas after therapy these 2 values were similar (20.3 +/- 4.3 vs 21.0 +/- 4.3 ml/kg/min; p = NS), indicating that patients were no longer limited by peripheral factors. Besides, VO2 leg increase after therapy was higher in patients in whom difference between VO2 arm + leg and VO2 leg was the greatest (i.e., in patients who were initially more limited by peripheral factors). Simultaneously, calf peak reactive hyperemia and circumference significantly increased, indicating an improvement in vascular dilating capacity and an increase in skeletal muscle mass. No significant modification occurred in the forearm. Thus, patients who improved the most after 3 months of quinapril therapy were those who were initially limited by peripheral factors. The restricting role of these factors was reduced after quinapril therapy.