Experiments were performed under Saffan anaesthesia on normoxic (N) rats and on chronically hypoxic rats exposed to 12% O₂ for 1, 3 or 7 days (1, 3, 7 CH rats): N rats routinely breathed 21% O₂ and CH rats 12% O₂. The 1, 3 and 7 CH rats showed resting hyperventilation relative to N rats, but baseline heart rate (HR) was unchanged and arterial pressure (ABP) was lowered. Femoral vascular conductance (FVC) was increased in 1 and 3 CH rats, but not 7 CH rats. When 1-7 CH rats were acutely switched to breathing 21% O₂ for 5 min, ABP increased and FVC decreased, consistent with removal of a hypoxic dilator stimulus that is waning in 7 CH rats. We propose this is because the increase in haematocrit and vascular remodelling in skeletal muscle help restore the O₂ supply. The increases in FVC evoked by acute hypoxia (8% O₂ for 5 min) and by infusion for 5 min of -calcitonin gene related peptide (-CGRP) which are NO-dependent were particularly accentuated in 1 CH, relative to N rats. The NO synthesis inhibitor L-NAME, increased ABP, decreased HR and greatly reduced FVC, and attenuated increases in FVC evoked by acute hypoxia and - CGRP, such that baselines and responses were similar in N and 1-7 CH rats. We propose that in the first few days of chronic hypoxia there is tonic NO-dependent vasodilatation in skeletal muscle that is associated with accentuated dilator responsiveness to acute hypoxia and dilator substances that are NO-dependent.