The stimulation by superantigens of T cells expressing an appropriate V beta chain results in a strong proliferative response that is followed by a state of energy specific for the antigen used. This model was used to continue our studies on immunoregulatory host neuroendocrine responses. We have recently found that four days after administration of the superantigen staphylococcal enterotoxin B (SEB) into mice, that is, at an early stage of the anergic phase, the decrease in the percentage of splenic CD4V beta 8 was accompanied by a decrease in the splenic concentration of the sympathetic neurotransmitter noradrenaline (NA) as compared to vehicle-injected mice. No comparable changes were detected in the kidney. At this point, blood levels of NA, adrenaline, and corticosterone were comparable in SEB- and vehicle-injected mice. We have also found that the decrease in splenic CD4V beta 8 cells was not observed in animals that had been chemically sympathectomized prior to the administration of the superantigen. These results indicate that the sympathetic response induced by SEB may have immunoregulatory implications.