The effects of restraint stress (RS) and the opioid antagonist, naltrexone, were evaluated on humoral immune responsiveness and gastric mucosal integrity in rats. RS for 24 h, but not 6 h, attenuated both the primary (PAR) and secondary antibody response (SAR) to sheep red blood cells (SRBC) after a single exposure to the stressor. Naltrexone (1 or 5 mg/kg) dose-dependently aggravated the effects of RS on anti-SRBC antibody titre in both PAR and SAR studies. Further, in rats sensitized with SRBC, RS (24 h), in addition to lowering the humoral antibody response, also induced gastric mucosal lesions. Both these responses were further aggravated with naltrexone pretreatment. These results are discussed in light of interactions between immune and visceral responses, and their regulation by endogenous opioids, during RS.