Long-term exercise training selectively alters serum cytokines involved in fever. Chronic exercise training has a number of effects on the immune system that may mimic the physiological response to fever. Female rats that voluntarily exercise on running wheels develop an elevated daytime core temperature after several weeks of training. It remains to be seen whether the elevation in daytime temperature involves inflammatory patterns characteristic of an infectious fever. We assessed whether chronic exercise training in the rat would alter levels of cytokines involved in fever. Female Sprague Dawley rats at 45 days of age weighing 90-110 g were divided into two groups (exercise and sedentary) and housed at an ambient temperature of 22( degrees )C. Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), iron, and zinc levels were analyzed. Rats underwent 8 weeks of exercise on running wheels. Exercise led to altered levels of some key cytokines that are involved in fever. Exercise animals had significantly higher IL-1beta levels and lower IL-10 levels compared to sedentary animals. Although IL-6 levels were slightly lower in the exercise animals, these levels were not significantly affected by training. TNF-alpha activity was similar in the two groups. Training also led to a slight increase in serum zinc and decrease in serum unsaturated iron binding capacity (UIBC). The data suggest that chronic exercise training evokes immune responses that mimic some, but not all, aspects of fever. This may explain why exercise leads to elevated daytime core temperature.