We have previously shown that social confrontation between aggressive fish (e.g., Tilapia) produces a suppression of several immunological parameters--nonspecific cytotoxicity and mitogen-stimulated proliferation in pronephric lymphocytes--in the subordinate fish. By using the opioid antagonist, naltrexone, we now demonstrate indirectly that this immunosuppression is in part mediated by the endogenous opioid system. Evidence is presented that naltrexone-mediated reversal of immunosuppression may be limited to the populations of the cytotoxic and T-cell lineages. The proliferative response to lipopolysaccharide is unaffected by naltrexone. Our data also demonstrate that serum from subordinate (immunosuppressed) fish is immunosuppressive in normal fish: an effect that can be reversed by naltrexone. These results support a link between the neuroendocrine and immune systems in these animals.