Unanesthetized, male rats were exposed to normal air (NA), or NA and a 4 h-exposure of He-O2 (79% helium, 21% oxygen) at ambient temperature (Ta) of 22 or - 10 degrees C. Blood samples from each individual were taken from a chronically implanted carotid cannula at 1) preexposure, 2) during exposure, 3) 2.5 h after exposure, and 4) 19-20 h after exposure. Exposure to He-O2 at 22 degrees C caused an increase in plasma free fatty acids (FFA) and corticosterone of 45% and 49%, respectively, with little change in plasma glucose and thyroxine. Exposure to He-O2 at 10 degrees C for 3 h invariably induced hypothermia with body temperature (Tb) decreased to 23.7 +- 0.5 degrees C (N = 10). During hypothermia, plasma glucose, FFA, and corticosterone were significantly higher (P LESS THAN 0.05) than those at preexposure and those after exposure to NA at -10 degrees C. During spontaneous recovery from hypothermia, at Ta = 19 degrees C and NA, glucose, corticosterone, and thyroxine returned to normal, but FFA remained significantly higher than at preexposure. The ability of animals to rewarm spontaneously from hypothermia and the quick return of metabolic substrates and hormones to normal after rewarming indicates the preservation of regulatory mechanisms for metabolism at depressed Tb when hypothermia is induced by He-O2 and cold.