Because metabolism is a determinant of the ventilatory chemosensitivity, we tested the hypothesis that the ventilatory response to acute and prolonged hypercapnia is adjusted to the circadian oscillations in oxygen consumption (VO2). Adult rats were instrumented for measurements of body temperature (T(b)) and activity by telemetry. Pulmonary ventilation (VE) was measured by the barometric method and VO2 by the flow-through method. In the acute experiments, 16 conscious rats entrained to a 12:12-h light (L)-dark (D) cycle (lights on 7:00 AM) were exposed to air, 2%, and then 5% CO2 in normoxia (30-45 min each) at 11:00 AM and 11:00 PM. In a separate group of seven rats, simultaneous recordings of all variables were made continuously for 3 consecutive days in air followed by 3 days in 2% CO2 in normoxia, in a 12:12-h L-D cycle (lights on 7:00 AM). In air, all variables were significantly higher at night, whether rats were studied acutely or chronically. Acute CO2 exposure had similar significant effects at 11:00 AM and 11:00 PM on VE (approximately 25 and 100% increase with 2 and 5% CO2, respectively) and VO2 (approximately 8% drop with 5% CO2), such that the hyperventilatory response (% increase in VE/VO2 from air) was similar at both times. Chronic CO2 breathing increased VE at all times of the day, but less so during the L phase (approximately 15 vs. 22% increase in L and D, respectively), when activity was lower. However, VO2 was reduced from the air level (approximately 10% drop) in the L, such that the VE/VO2 response was similar between L and D. The same result was obtained when the VE/VO2 response was compared between the L and D phases for the same level of activity. These results suggest that, throughout the day, the hypercapnic hyperpnea, whether during acute or prolonged CO2, is perfectly adjusted to the metabolic level.