The purpose of this study was to examine effects of repeated whole-body hyperthermia on the growth of carcinogen-induced rat mammary carcinomas. Female Sprague-Dawley rats were treated intragastrically with a single dose (100 mg/kg) of the carcinogen 7,12-dimethylbenzanthracene (DMBA) at 2 months of age. Subsequently, when each rat had a minimum of one palpable mammary carcinoma, the animals were divided into two groups, one to receive hyperthermia treatments and the other to serve as controls. The hyperthermia-treated rats received 14-20 1-hour episodes of whole-body hyperthermia (averaging 41.4 degrees C, colonic) over a period of 3-4 weeks. The animals were anesthetized with sodium pentabarbital during these treatments to suppress their thermoregulation and to minimize stress mediated by higher brain functions. Their temperature was raised by exposure to high air temperatures. Control rats were anesthetized on the same schedule, and with the same doses of barbital, as hyperthermia-treated rats, but during anesthetization were placed at lower air temperatures such that their body temperatures remained normal. Tumor volumes were measured once per week. By the end of the first week, hyperthermia had suppressed carcinoma growth: whereas 78% of control carcinomas had increased in volume, 73% of hyperthermia-treated ones had decreased in volume. The average volume of mammary carcinomas in hyperthermia-treated rats after 1 week was significantly smaller than the average volume of mammary carcinomas in control rats: 0.34 vs. 0.66 cm3 (effects of differences in initial volume statistically removed). This difference had enlarged by the end of four weeks to 0.11 cm3 (hyperthermia-treated) vs. 0.80 cm3 (control). Overall, this study provides compelling evidence that whole-body hyperthermia in the range of 41-42 degrees C suppresses growth of DM-BA-induced rat mammary carcinomas, and it describes a technique for hyperthermia induction in which stresses specific to hyperthermia are minimized or avoided.