Little is known about the effects of physical activity (i.e., exercise training) on susceptibility to environmental toxicants. Chlorpyrifos (CHP), an organophosphate (OP) insecticide, affects thermoregulation, causing an acute period of hypothermia followed by a delayed fever. Since exercise conditioning alters the thermoregulatory responses of rodents, this study examined whether exercise training would alter the thermoregulatory response to repeated CHP administration in the female Sprague-Dawley rat. Core temperature (T(c)) and motor activity (MA) were monitored by radiotelemetry in rats housed at an ambient temperature (T(a)) of 22 degrees C. The rats either were provided with continuous access to running wheels (exercise group) or were housed in standard cages without wheels (sedentary group). The exercise group rats ran predominantly at night with an average of 7.6 km/24h. After 8 weeks the rats in both groups were gavaged daily with corn oil or 10mg/kg CHP (dissolved in corn oil) for 4 days. CHP induced an immediate hypothermic response followed by a delayed fever throughout the next day in the sedentary group rats after the first three doses of CHP. The exercise group rats showed no hypothermia after the first dose of CHP. However, they became hypothermic after the second and third doses of CHP. The exercise group rats developed a smaller daytime fever after each dose of CHP compared to the sedentary group rats. Overall, exercise training attenuated the hypothermic and febrile effects of repeated CHP. Thus, the data suggest that a sedentary lifestyle may increase the sensitivity to OP insecticides. Exercise training was also associated with a more rapid recovery of plasma cholinesterase activity.