The purpose of the study was to assess the effect of genetic strain on the acute and long-term thermoregulatory response to the neurotoxicant, trimethyltin (TMT) in rats of the Long-Evans (LE) and Fischer 344 (FCH) strains. In one study basic thermoregulatory responses including colonic temperature (Tc), metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), and thermal conductance (Cd) were measured in both rat strains at ambient temperatures (Ta) of 10, 28, and 37 C. It was found that the LE rat has a significantly higher Tc when it is measured in their home cage. Because of its smaller mass the FCH rat has a higher MR at all Ta's. The FCH rat also has a greater rate of EWL during exposure to a Ta of 37 C. Following i.v. administration of 8.0 mg/kg TMT both rat strains become significantly hypothermic; however, the effect differed significantly between the strains. At 26 to 34 days after TMT exposure thermoregulatory responses at Ta's of 10 to 37 C were generally similar to that of the saline controls. However, there was a significant elevation in MR and MA of the TMT-treated FCH rat which merits further study. Overall, it appears that autonomic thermoregulatory responses measured 26 to 34 days after TMT are near normal in the FCH and LE rat strains.