Exercise stimulates the release of interleukin-6 (IL-6). Aims of the study were to: (a) analyse the IL-6 response to exercise in power (n = 7) and endurance athletes (n = 13); (b) determine the effects of the IL-6 production on mechanical and myoelectric fatigue; (c) evaluate the relationship between IL-6 and adrenocortical responses. EMG variables (conduction velocity, mean power frequency, average rectified value), ACTH, cortisol, DHEA, IL-6, myoglobin, and lactate were analysed before and after an isokinetic exercise. The exercise elicited significant mechanical and myoelectric fatigue as well as significant biochemical responses. Power athletes showed IL-6 and lactate responses higher than endurance athletes. The correlation analyses showed that the greater the mechanical fatigue, the greater the increases in lactate and IL-6. No correlations were found between IL-6 and EMG variables. No relationships were found between IL-6 and cortisol, after correction for ACTH levels. In conclusion, the muscular IL-6 production, as inferred by its circulating levels, had no detectable effects on the myoelectric manifestations of fatigue and the cortisol response to exercise was not related to the amount of circulating IL-6, but only to the activation of ACTH secretion.