No current theory of the mechanisms involved in the pathophysiology of rheumatoid arthritis (RA) explains its important clinical features. We hypothesize that neural mechanisms are involved in this pathophysiology and they explain at least 3 clinical features: specific high risk joints are more likely to develop arthritis; specific high risk joints have more severe arthritis; and RA is bilaterally symmetric. If our hypothesis is correct, it will provide a rationale for the development of new therapies for what is now an inadequately treated disease.