Patients with seronegative and patients with seropositive rheumatoid arthritis (RA) have clinical, genetic, and immunologic differences. This study was undertaken to determine whether the two populations differ radiologically. Seventeen patients with seronegative RA were closely matched with seropositive control subjects. Radiographs of the hands and wrists were studied blindly, and disease severity was quantified with use of a modification of the Beaver Creek grading sheet. The following distinguishing features were also evaluated: osteosclerosis, new bone formation, carpal predominance, ankylosis (fusion), symmetry, and classical erosions. Seropositive patients had more severe disease, with larger and more numerous erosions, while the seronegative group had more osteosclerosis, carpal predominance, fusion, and new bone formation. Symmetry was equal in both groups. Although there were definite quantitative and qualitative differences between the two populations, radiologists should be cautious in using these criteria because of the great deal of overlap between the two groups.