The responses of arterioles and venules to systemic hypoxia (fractional inspired O2 concentration 0.10) were determined for the rat cremaster muscle that was positioned with intact nerve and vascular supplies in a tissue bath that had controlled pH, O2 tension (PO2), CO2 tension (PCO2), and temperature. Blood pressure and heart rate were decreased significantly during systemic hypoxia. First- and second-order arterioles actively constricted during systemic hypoxia, whereas most first-, second-, and third-order venules had biphasic responses (dilation followed by constriction). There were no significant differences in the active arteriolar responses to systemic hypoxia when cremaster bath pH was altered from 6.9 to 7.2, or when bath PCO2 was changed from 60 +/- 2.2 to less than 5 mmHg; but, there was significantly greater arteriolar constriction with high bath PO2 (139 +/- 1.3 mmHg) in comparison to low bath PO2 (4.5 +/- 0.5 mmHg). Decreased bath pH, decreased PO2, and increased PCO2 had no effect on the dilation responses of first-, and second-, and third-order venules to systemic hypoxia; however, these bath alterations attenuated the constriction responses of third-order venules. alpha-Adrenergic receptor blockade did not alter the arteriolar responses to systemic hypoxia. Our data indicate 1) that there is a centrally mediated stimulus for constriction of first-order arterioles during systemic hypoxia, 2) that changes in local cremaster PO2, but not PCO2 or pH, can attenuate this centrally mediated arteriolar constriction, and 3) that the centrally mediated arteriolar constriction does not involve alpha-adrenergic receptors.