The role of endogenous opioids in systemic and renal circulatory changes during combined acute hypoxemia and hypercapnic acidosis was evaluated in seven conscious female mongrel dogs in rigid sodium balance. Animals were studied 2 wk apart in separate protocols of combined acute hypoxemia (arterial O2 tension = 33 +/- 1 mmHg) and hypercapnic acidosis (arterial CO2 tension = 56 +/- 1 mmHg, pH = 7.19 +/- 0.01) of 40 min duration during 1) naloxone, 5 mg/kg iv bolus followed by an intravenous infusion of 5 mg.kg-1.h-1, and 2) vehicle (5% dextrose in water) alone. Systemic circulatory changes during the combined acute blood-gas derangement including increased mean arterial pressure, heart rate, and cardiac output and decreased total peripheral resistance were comparable between naloxone and vehicle treatments. However, in striking contrast to the brief fall in renal hemodynamic function during combined acute hypoxemia and hypercapnic acidosis with vehicle, naloxone administration during the combined acute blood-gas derangement resulted in a sustained decrease in effective renal plasma flow, glomerular filtration rate, and filtered sodium load and enhanced rise in circulating norepinephrine and epinephrine. Changes in plasma renin activity were comparable between vehicle and naloxone protocols except that plasma renin activity increased from the first to the second 20-min periods of combined hypoxemia and hypercapnic acidosis with naloxone. These observations suggest that endogenous opioids may contribute to preservation of renal hemodynamic function during acute blood-gas derangements, possibly through attenuation of sympathetic nervous system and renin-angiotension activation.