The rate of formation of expired14CO2from histidine,14C-labeled in the carboxyl group (C-His) or in the imidazole ring (R-His), and also from14C-ring labeled urocanic acid (R-Uro) has been measured in rats subjected to restraint and cold stress. The rate of expiration of14CO2by restrained rats given C-His was significantly increased over control values; that from R-His was decreased. When restrained rats were also exposed to cold (4 °C), the rate of formation of14CO2from C-His decreased; that from R-His now showed an even greater decrease than when the measurements were made at room temperature. The rate of formation of labeled carbon dioxide from R-Uro was not altered significantly by these stressful procedures.Parallel measurements of the enzyme activities of histidine catabolism in rats restrained at room temperature for 2 h revealed no alteration in histidase activity of liver and lungs, but there was a marked increase in the histidine decarboxylase activity of stomach. Exposure of rats to cold over 1 h during the restraint of movement also resulted in enhanced histidine decarboxylase activity but of a lesser degree; 2 h of cold exposure during restraint abolished the difference between the control and stressed animals that had been observed at room temperature.The serum histidine concentration was measured 30 min after the intraperitoneal administration of 500 mg of histidine per kilogram body weight to rats. Both groups of stressed animals (restraint at room temperature, restraint in the cold) had much higher levels than observed in the corresponding controls. These results suggest that the increased histidine decarboxylase activity of stomach that develops under the stress of restraint is associated with a compensatory decrease in the rate of histidine uptake from the blood into the tissues. The data obtained for the rate of formation of expired14CO2have been interpreted in this light.