Muscle fatigue is a prominent symptom in patients with chronic heart failure (CHF). To determine whether it results from an intrinsic abnormality of vasodilating capacity of the vasculature in exercising muscle, we studied local forearm blood flow (FBF) during exercise in 13 patients with severe CHF and in eight normal untrained subjects of similar age. Intermittent forearm static exercise was performed by squeezing a hand dynamometer for 5 seconds, three times per minute, for 5 minutes at 15%, 30%, and 45% of maximum voluntary contraction. FBF was measured by mercury-in-rubber strain gauge venous plethysmography at baseline before exercise and during the last 3 minutes of each exercise stage. Exercise was repeated after 24 hours of inrtravenous administration of milrinone in the patients with CHF. FBF increased with forearm exercise in a reproducible manner during 24 hours in the normal subjects: rest, 2.54 ± 0.23 (0 hours), 2.90 ± 0.23, (24 hours); 15%, 7.25 ± 0.92, 5.85 ± 0.56; 30%, 9.20 ± 1.08, 10.05 ± 0.85; 45%, 14.62 ± 1.64, 13.85 ± 1.09 ml/100 ml/min; p = NS, 0 versus 24 hours. In patients with CHF, FBF was reduced at baseline compared with normal subjects (1.70 ± 0.15 ml/100 ml/min, p < 0.05), but no significant differences from normal subjects were observed during exercise (15%, 5.04 ± 0.65; 30%, 7.64 ± 0.99; 45%, 12.56 ± 1.20 ml/100 ml/min). Peak exercise blood flow was correlated negatively with central venous pressure (r = -0.65, p < 0.05) and positively with right ventricular ejection fraction (r = 0.59, p < 0.05). Twenty-four hours of intravenous milrinone administration did not significantly alter FBF during exercise. Similar results were seen for forearm vascular resistance and percent forearm oxygen extraction. The exercise protocol did not significantly increase cardiac output in CHF patients (n = 4) (baseline, 3.93 ± 0.77; 45%, 4.05 ± 0.63 l/min; p = NS). Because FBF was not significantly reduced during submaximal forearm exercise in patients with severe CHF or improved by milrinone therapy, we conclude that 1) a reduction in vasodilator capacity is not limiting at submaximal work loads, and 2) an improvement in submaximal functional performance with milrinone may not be secondary to increased intrinsic vasodilation of muscle vasculature during exercise. Alternative explanations for muscle fatigue during whole-body exercise may include inadequate cardiac output response or abnormalities in muscle metabolism.