Rats exposed to chronic stress demonstrate an enhanced motor response to psychostimulants, such as cocaine. This behavioral cross-sensitization between stress (repeated mild footshock) and cocaine (15 mg/kg, ip) is associated with an increase in extracellular dopamine in the nucleus accumbens, but a decrease in the prefrontal cortex. To determine a role for the hypothalamic-pituitary-adrenal axis in sensitization, rats were adrenalectomized prior to administering repeated cocaine injections. One and twelve days after discontinuing repeated cocaine, rats were challenged with acute cocaine. Adrenalectomy blocked the cocaine-induced sensitization observed in sham animals, but both the sham and adrenalectomized rats demonstrated behavioral sensitization to cocaine after twelve days of withdrawal. These data argue that while long-term alterations in dopamine transmission may be an important neurochemical substrate of stress and psychostimulant-induced sensitization, the hypothalamic-pituitary-adrenal axis may not have a necessary role.