We investigated the effect of prolonged hypercapnia on human thermoregulation during immersion of seven male subjects in a 15 degrees C water bath until their esophageal temperature dropped to 35 degrees C or until 1 h had elapsed. In the control trial, subjects inspired room air, whereas in the other trial the inhaled gas mixture was a 4% CO2:20% O2:76% N2 gas mixture. Oxygen uptake (VO2, liter.min-1), inspired minute ventilation (VI, liter.min-1), esophageal temperature (Tes, degree C), mean unweighted skin temperature (Tsk, degree C), mean heat flux (Q, W.m-2), and electromyographic (EMG, mV) activity of the trapezius muscle were recorded. VO2 and integrated EMG (IEMG) activity were used as the primary indicators of shivering thermogenesis. There was a tendency for elevated VO2, albeit not significant, in the CO2 trial compared to the air trial. We observed no significant differences in the IEMG between the air and CO2 trials. These results suggest that prolonged inhalation of a gas mixture containing 4% CO2 does not have a significant inhibitory effect on shivering thermogenesis and does not enhance the cooling rate of the body core. The absence of any shivering attenuation is most likely due to the small blood PCO2 increase incurred by inhalation of 4% CO2, compensation of hypercapnic-induced respiratory acidosis, and a strong thermal drive from core and peripheral regions. It is unlikely that elevated PICO2 levels contribute significantly to the etiology of hypothermia in divers.