The specificity of antiperinuclear factor (APF) for patients with rheumatoid arthritis (RA) is well documented. It is unknown whether detection of these antibodies adds information to the detection of rheumatoid factor (RF). In a group of 132 patients with RA, 94 were RF positive. Of the 38 patients persistently negative for RF, 14 (37%) were positive for APF. These 14 proved to have a disease course similar to that of RF positive patients. This similarity was shown most impressively by radiological progression of the disease, and to a lesser extent, by the medication needed to control the disease and the number of extraarticular manifestations. No significant correlation was shown between APF and antinuclear antibodies. Among the RF positive patients with their generally poorer prognosis, APF identified the worst affected. Our study suggests that APF in serum of patients with RA is associated with a poor disease outcome, especially in RF negative patients.