Hypothalamic secretion of corticotropin releasing hormone (CRH) triggers the secretion of pituitary ACTH and antiinflammatory adrenal corticosteroids. CRH is also secreted in local inflammatory sites such as the arthritic joint, but its action appears to be proinflammatory. This review notes the complex interrelationships of the nervous, endocrine, immune and inflammatory systems and suggests that abnormalities in these interactions may play a role in susceptibility to rheumatoid arthritis and various animal models of autoimmune diseases.