Neonatal thymectomy (NTX) of BALB/c mice between days 1 and 3 post-birth leads to a high incidence of autoimmune gastritis involving T cells and autoantibodies. Although progress has been made in understanding various immunological events associated with that disease process, much remains to be learned about the regulatory factors which control autoimmune gastritis. In this study we have examined the potential for neuroendocrine hormones of the hypothalamus-pituitary-thyroid (HPT) axis to alter the outcome of experimental autoimmune gastritis in NTX mice. As reported here, thyroxine administered to young adult NTX mice during an active phase of disease development dramatically reduced the incidence of gastritis and the overall severity of disease, and lowered the levels of anti-parietal cell antibodies. In contrast, treatment of young NTX mice with thyroxine or other HPT hormones prior to the onset of disease had no beneficial effect on gastritis, but instead resulted in significantly higher anti-parietal cell antibody levels compared to non-hormone-treated NTX mice or to NTX mice treated as adults. Reverse transcriptase spectratype analyses of 22 Vbeta gene junctional sites revealed pronounced oligoclonality and limited junctional diversity in stomach lymphocytes from untreated NTX mice compared to normal mice or thyroxine-treated NTX mice. These findings identify a set of dynamic immune-endocrine interactions, linked to critical development-dependent events, that are involved in the expression and regulation of peripheral autoimmunity.