The effects of cocaine, stress, and the combination of cocaine and stress on proliferative responses to mitogens in vitro were examined in rats. In this paradigm, hypothalamic dopamine and norepinephrine were measured to examine whether catecholamine levels relate to changes in immune function. Cocaine, stress, and cocaine plus stress decreased cellular immune function to Con A mitogen compared with a control group. Hypothalamic dopamine levels were inversely related to immune proliferation to lipopolysaccharide (LPS) mitogen. The results are discussed in terms of the deleterious effects of cocaine and stress and possible mechanisms for cocaine and stress induced immune suppression.