In the laboratory rat, inhalation (30 s) of high (> 70%) CO2 concentrations resulted in short-term (1-3 min) anesthesia, followed by a prolonged (up to 60 min) mild antinociception. Exposure to 100% CO2 resulted in significant thermal (hot-plate, 52 degrees, and tail-flick) and mechanical (tail-pinch, 886 g force) antinociception. Control animals, placed in the same chamber filled with air, showed no such effects. Rats exposed to 70% CO2 exhibited effects on the hot plate comparable to those seen after inhalation of 100% CO2, indicating that the response is not due to CO2-induced hypoxia. Additionally, recovery from halothane-induced anesthesia of comparable duration did not result in antinociception, confirming that anesthesia alone is not sufficient to produce the effect. Pretreatment with the opiate antagonist naltrexone (0.1-10 mg/kg i.p.) did not diminish the CO2-induced antinociception, suggesting that endogenous opioids are not obligatory in the mechanism of this response. Furthermore, hypophysectomy abolished hot-plate antinociception in animals exposed to 100% CO2 while sham-treated controls exhibited a pattern of hot-plate responses similar to that reported above. Taken together, these findings show that: (1) recovery from CO2-induced anesthesia results in a prolonged mild antinociception, detectable with thermal and mechanical nociceptive tests; and (2) this response may represent a novel from of environmentally induced antinociception, mediated by a non-opiate hormonal substance.