Susceptibility to enteric infection with Salmonella was studied in mice housed at different temperatures. The oral doses of S. typhimurium SR-11 and RIA, which caused 50% mortality in animals at 10 C, were about 1/30 and 1/100 of the respective values at 23 C, and that of an avirulent strain of S. enteritidis was also lower in the cold-exposed mice. The frequency of mortality due to Salmonella infection was essentially the same in mice exposed to 34 to 23 C. The divergent responses in the cold and heat probably stem from basic differences in the physiological changes mediated by the two extremes. The pattern and extent of change in weight and rectal temperature were the same among infected mice housed at 10 and 23 C and controls at 10 C, but differed from controls at 23 C. The incidence of Salmonella in samples of liver-spleen, lung, colon, blood, or feces was similar among infected mice housed at 10 and 23 C during a 14-day period of observation. The increased frequency of mortality in cold-exposed infected animals is not due to alterations in invasiveness of the bacteria nor to greater impairment of the thermoregulatory capacity of the mice. It may be attributable, in part at least, to a greater effectiveness of Salmonella toxins as metabolic poisons at low temperatures.