The aims of the present study were to evaluate how acute systemic hypoxia affects O2 delivery to skeletal muscle and muscle O2 consumption (VO2) of the rat and to establish how these relationships are altered by chronic systemic hypoxia. Thus, the effects of breathing different concentrations of O2 (air, 12% and 8% O2) upon oxygen delivery and VO2 were studied in hindlimb muscles of control, normoxic (N) rats and of rats that had been made chronically hypoxic in a chamber at 12% O2 for 3-4 weeks (CH) rats. Under anaesthesia, arterial blood pressure, femoral blood flow (FBF), arterial O2 content (Ca,O2) and venous O2 content in the efflux from hindlimb were measured. In N rats, changing the inspirate from air to 12% and 8% O2 for 5 min each, reduced Ca,O2 from 20 +/- 0.3 ml (100 ml)-1 in air to 13 +/- 1.0 ml (100 ml)-1 in 8% O2. FBF did not change significantly (1.7 +/- 0.1 ml min-1 in air) so that O2 delivery to hindlimb muscles fell from 0.28 +/- 0.07 to 0.16 +/- 0.02 ml min-1 in 8% O2. Nevertheless, the VO2 of hindlimb muscle was well maintained: 0.06 +/- 0.02 ml min-1 in air and 0.08 +/- 0.02 ml min-1 in 8% O2. In CH rats breathing 12% O2, Ca,O2 (23 +/- 1.0 ml (100 ml)-1) was comparable to that of N rats breathing air, due to an increase in haematocrit, as were FBF (1.6 +/- 0.2 ml min-1) and O2 delivery (0.39 +/- 0.05 ml min-1). However, VO2 was 2.5-fold greater in CH rats (0.16 +/- 0.03 ml min-1). As in N rats, FBF was well maintained at 1.7 +/- 0.2 and 1.6 +/- 0.2 ml min-1 in 8% O2 and air, respectively. Further, VO2 was also well maintained, at 0.17 +/- 0.02 and 0.12 +/- 0.02 ml min-1 in 8% O2 and air, respectively. These results suggest that, contrary to previous reports, muscle VO2 of the rat is independent of O2 delivery over a wide range of O2 delivery values. They also suggest that muscle VO2 of CH rats is similarly independent of O2 delivery. The novel finding that muscle VO2 has a greater absolute value in CH rats can, we propose, be explained by an increase in VO2 of the vasculature rather than of the skeletal muscle fibres and reflects increased biosynthetic activity of the vessel walls and/or vascular remodelling.