Rat skeletal muscle O2 uptake (VO2) has been reported to be supply dependent even at normal blood flow rates. To find the point at which whole-animal VO2 became dependent on total O2 transport (TOT), intact anesthetized rats were ventilated under hypoxic, normoxic, and hyperoxic conditions while either normovolemic or hypovolemic. In this manner, TOT (cardiac output X arterial O2 content) was varied over a range of 5-80 ml . kg-1 . min-1 . VO2 was measured in a closed-circuit, double servospirometer system. O2 contents were measured in carotid artery and right heart blood. Arterial PCO2, pH, and rectal temperature were kept within normal limits. Above a TOT of 23 ml . kg-1 . min-1, reciprocal changes in O2 extraction and cardiac output maintained VO2 independently of TOT (VO2 = 17.9 +/- 1.3 ml . kg-1 . min-1). Below a TOT of 23 ml . kg-1 . min-1, Vo2 became linearly dependent upon TOT. For TOT between 5 and 16 ml . kg-1 . min-1, VO2 = 0.89 + 0.78 TOT (r = 0.98). These data indicate that above a critical TOT of approximately 23 ml . kg-1 . min-1, VO2 in anesthetized rats does not depend on TOT.