BACKGROUND: Carbon dioxide decreases halothane minimum alveolar concentrations (MAC) in dogs when PaCO2 exceeds 95 mm Hg. We sought to confirm these findings for several potent inhaled anesthetics in rats. METHODS: Groups of eight rats were anesthetized with halothane, isoflurane, or desflurane. MAC was determined for each anesthetic alone, and then with increasing concentrations of inspired CO2. A fourth group was given CO2 alone to determine the MAC of CO2. RESULTS: Increasing inspired CO2 concentrations produced a linear dose-dependent decrease in MAC of each potent inhaled anesthetic. With elimination of CO2, the MAC of isoflurane and desflurane returned to the original MAC. As determined by extrapolating these data to 0% of the inhaled anesthetic, the MAC of CO2 was approximately 50% of 1 atm. Given alone, CO2 proved lethal. CONCLUSIONS: Unlike dogs, no threshold for the CO2-MAC response arose with halothane, isoflurane, or desflurane in rats. The ED50 for CO2 is also approximately 50% greater in rats than reported in dogs.