To compare the physiological response to a cocaine-exercise challenge in cocaine-conditioned animals with that of acute-cocaine animals, rats were injected i.p. with either cocaine (20 mg·kg−1) or saline, twice daily for 14 consecutive days. On the 15th day (test day) cocaine-conditioned rats received an i.v. injection of cocaine (5 mg·kg−1) (chronic group). One-half of the chronic saline rats also received the cocaine injection (acute group), while the other half received saline (saline group). Immediately after injection, all rats were either rested or exercised (22 miming−1, 10% grade) for 30 min. For most parameters there was no difference between the responses of the chronic and acute cocaine groups at rest or to the cocaine-exercise challenge. During exercise, both cocaine groups had similarly higher lactate values than the saline animals (P< 0.05). Both groups had similarly greater reductions in glycogen content of the white and red vastus muscles than occurred in the saline group; and both groups had similar increases in corticosterone. In contrast, cocaine-conditioned animals had a greater rise in norepinephrine (P< 0.059) and epinephrine (P< 0.001) in response to cocaine-exercise than did the acute group. The mechanism responsible for the exaggerated catecholamine response in the chronic cocaine animals is unknown.