A case control study of 50 rheumatoid factor positive (RA+) and 50 rheumatoid factor negative (RA-) patients with rheumatoid arthritis has been carried out. As expected, the RA+ group has significantly more nodules and vasculitis. In terms of clinical joint involvement, the RA- had large-joint involvement. Radiologically, seropositive disease was characterized by more severe involvement of the metacarpophalangeal joints of the thumb and index fingers and in all the metatarsophalangeal joints of the feet. There was no difference either clinically or radiologically between the two groups in terms of symmetry of joint disease or wrist involvement. Of special interest was the finding that the prevalence of HLA-DR4 was elevated to the same degree in both groups but that genetic markers for ankylosing spondylitis and for psoriasis (HLA-B27 and Cw6 respectively) were similar in both groups and not increased above control population levels. It is concluded that the entity defined as RA includes patients with and without rheumatoid factor (RF) in their serum and that this determines differences in disease expression. Whether these differences are the consequences or the cause of RF cannot be concluded on the basis of this study.