Based on observed phenotypic differences in growth and ACTH responses to stress in Sprague Dawley rats obtained from different vendors, we ran head-to-head comparisons on rats obtained from three different vendors, Harlan, Charles River, and Simonsen, with respect to baseline phenotypic differences and a metabolic feedback hypothesis of hypothalamo-pituitary-adrenal (HPA) regulation. Charles River and Harlan rats gained weight faster than Simonsen rats, but chow intake standardized for body weight was not increased, consistent with their greater caloric efficiency. Weight gain was inversely related with mean daily temperatures, without differences in activity levels. Half of the animals given lard and 32% sucrose solutions in addition to chow increased caloric intake and core temperature, decreased caloric efficiency, and increased fat depots, leptin, and in Simonsen rats, insulin. A 5-day regimen of once-daily 2-h restraint decreased feeding and caloric efficiency. Rats from two vendors with the availability of sucrose and lard, Charles River and Simonsen, showed blunted HPA responses to restraint compared to chow controls, whereas the Harlans exhibited no adrenocortorticotropin (ACTH) response and an amplified adrenocortical response on the high-energy diet compared to chow controls. Substantial phenotypic differences exist between Sprague Dawley rats from different vendors with respect to metabolism and HPA function. The metabolic feedback hypothesis was supported in two of the three vendors' rats.