We sought to determine whether chronic exposure to intermittent hypoxia (CIH) increases sympathetic responsiveness to subsequent chemoreflex stimulation. Sprague-Dawley rats were exposed to 30 days of CIH: exposure chamber %O2 [fractional concentration of chamber O2 (FcO2)] nadir 6.5-7% with return to 21% each minute for 8 h/day during the diurnal sleep period (Exp group). Sham controls (SC group) were similarly handled but kept at 21% FcO2 and compared with unhandled controls (UC group). Rats were then anesthetized with urethan, and preganglionic cervical sympathetic activity (CSA), diaphragm electromyogram, arterial pressure, and electrocardiogram were recorded while the rats were spontaneously breathing 100% O2, room air, 10% O2, 12% CO2, and 10% O2-12% CO2. CSA and heart rate were also recorded during phenylephrine infusion to assess baroreceptor function. Mean arterial pressure was significantly greater in Exp than in SC and UC rats during all conditions (P < 0. 05). A vasopressor response to 10% O2-12% CO2 was observed only in Exp rats. CSA was greater in Exp than in SC and UC rats during 10% O2, 12% CO2, and 10% O2-12% CO2 but not during room-air exposure. A significant increase in CSA compared with room air was noted during 10% O2, 12% CO2, and 10% O2-12% CO2 in Exp but not in SC or UC rats. No differences in baroreceptor function were observed among groups. We conclude that CIH leads to increased sympathetic responsiveness to chemoreflex stimulation.