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 (O₂). Adult rats were instrumented for measurements of body temperature (T_b) and activity by telemetry. Pulmonary ventilation (E) was measured by the barometric method and O₂ 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 E (~25 and 100% increase with 2 and 5% CO₂, respectively) and O₂ (~8% drop with 5% CO₂), such that the hyperventilatory response (% increase in E/O₂ from air) was similar at both times. Chronic CO₂ breathing increased E at all times of the day, but less so during the L phase (~15 vs. 22% increase in L and D, respectively), when activity was lower. However, O₂ was reduced from the air level (~10% drop) in the L, such that the E/O₂ response was similar between L and D. The same result was obtained when the E/O₂ 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.