Streptococcal cell wall arthritis in rats is an experimental model that closely resembles rheumatoid arthritis in humans. Investigations in progress are focused on defining the pathogenesis of this model disease by characterizing arthritis-susceptible and arthritis-resistant rat strains, specifically Lewis (LEW/N) and Fischer (F344/N) inbred rats. During the past year, new data were generated directly implicating platelet derived growth factor, fibroblast growth factor and corticotropin releasing hormone in arthritic process. Interestingly, we observed that LEW/N rats produce abundant CRH in the joint but fail to upregulate CRH production in the hypothalamus. F344 rats were just the opposite. In addition, we observed that inflammatory disease-prone, hypothalamic CRH deficient LEW rats produced high levels of hypothalamic arginine vasopressin. Again, the F344 rats were just the opposite. These data support are view that the neuroendocrine, immune and inflammatory systems are closely interwined and may play a role in the susceptibility to autoimmune disease.