We have investigated the relationship between O2 delivery (DO2) and O2 consumption (VO2) in hindlimb muscle of anaesthetised rats during progressive systemic hypoxia. Since muscle vasodilatation that occurs during hypoxia is nitric oxide (NO) dependent, we examined the effects of the NO synthase (NOS) inhibitor nitro-L-arginine methyl ester (L-NAME). In control rats (n = 8), femoral vascular conductance (FVC) increased at each level of hypoxia. Hindlimb DO2 decreased with the severity of hypoxia, but muscle VO2 was maintained until the critical DO2 value (DO2,crit) was reached at 0.64 +/- 0.06 ml O2 min-1 kg-1; below this VO2 declined linearly with DO2. This is a novel finding for the rat but is comparable to the biphasic relationship seen in the dog. In another group of rats (n = 6), L-NAME caused hindlimb vasoconstriction and attenuated the hypoxia-evoked increases in FVC DO2 was so low after L-NAME administration that VO2 was dependent on DO2 at all levels of hypoxia. In a further group (n = 8), femoral blood flow and DO2 were restored after L-NAME by infusion of the NO donor sodium nitroprusside (20 g x kg(-1) x min(-1). Thereafter, hypoxia-evoked increases in FVC were fully restored. Nevertheless, DO2,crit was increased relative to control (0.96 +/- 0.07 ml O2 min(-1) x kg(-1), P < 0.01). As NOS inhibition limited the ability of muscle to maintain VO2 during hypoxia, we propose that hypoxia-induced dilatation of terminal arterioles, which improves tissue O2 distribution, is mediated by NO. However, since the hypoxia-evoked increase in FVC was blocked by L-NAME but restored by the NO donor, we propose that the dilatation of proximal arterioles is dependent on tonic levels of NO, rather than mediated by NO.