To determine the significance of nodules in rheumatoid arthritis, we reviewed the medical records of 420 patients who underwent standardized clinical, laboratory, and radiological investigations during a hospitalization for rheumatoid arthritis between January 1, 1981 and December 31, 1994. Sixty-six patients (16%) had nodules and 354 (84%) did not. Age and gender distributions were similar in the two groups. Disease duration was significantly longer in the nodular than in the nonnodular group (11.3 +/- 9.4 years versus 7.6 +/- 7.3 years; P = 0.0003). When patients were stratified into five-year disease duration groups, dryness of the eyes and mouth was found to be more common in the nodular group, with the difference being largest during the first five years. Patients with nodules were more likely to have vasculitis irrespective of disease duration (odds ratio, 6.08; P = 0.028). Lee's and Ritchie's indices and radiographic alterations were more severe in the nodular group, whereas tests for inflammation were not significantly different. Patients with rheumatoid factors accounted for a larger proportion of the nodular than of the nonnodular group (odds ratio 2.48; P = 0.017). When patients were dichotomized based on latex test results, nodules were not significantly associated with antiperinuclear factor or antikeratin antibodies, whereas patients with nodules were significantly more likely to have vasculitis (odds ratio 5.3; P = 0.035), antinuclear factors (odds ratio 1.82; P = 0.043), and cryoglobulinemia (odds ratio 4.86; P = 0.0029). As compared with nonnodular rheumatoid arthritis, nodular rheumatoid arthritis was associated with more severe extraarticular disease, faster radiographic progression and a greater likelihood of rheumatoid factor and antinuclear antibody production. Each of these characteristics was associated with the presence of nodules independently from disease duration and rheumatoid factor positivity.