We hypothesized that reducing arterial O-2 content (Ca-O2) by lowering the hemoglobin concentration ([Hb]) would result in a higher blood flow, as observed with a low PO2, and maintenance of O-2 delivery. Seven young healthy men were studied twice, at rest and during two-legged submaximal and peak dynamic knee extensor exercise in a control condition (mean control [Hb] 144 g/l) and after 1-1.5 liters of whole blood had been withdrawn and replaced with albumin (mean drop in [Hb] 29 g/l (range 19-38 g/l); low [Hb]}. Limb blood flow (LBF) was higher (P < 0.01) with low [Hb] during submaximal exercise (i.e., at 30 W, LBF was 2.5 +/- 0.1 and 3.0 +/- 0.1 l/min for control [Hb] and low [Hb], respectively; P < 0.01), resulting in a maintained O-2 delivery and O-2 uptake for a given workload. However, at peak exercise, LBF was unaltered (6.5 +/- 0.4 and 6.6 +/- 0.6 l/min for control [Hb] and low [Hb], respectively), which resulted in an 18% reduction in O-2 delivery (P < 0.01). This occurred despite peak cardiac output in neither condition reaching >75% of maximal cardiac output (similar to 261/min). It is concluded that a low Ca-O2 induces an elevation in submaximal muscle blood flow and that O-2 delivery to contracting muscles is tightly regulated.