OBJECTIVE: To analyze the relationship between lymphocyte subsets, different rheumatoid factor (RF) isotypes, and clinical features in patients with rheumatoid arthritis (RA). METHODS: Patients with established RA (n = 95) were examined clinically and blood samples were collected for measurements of RF by ELISA and for analysis of lymphocyte subsets by flow cytometry. RESULTS: IgA RF positive patients had more severe disease and higher prevalence of extraarticular manifestations than the other patients. Patients with elevated IgA RF had a higher percentage of CD5+ B cells and of CD4+CD45RO+ T cells compared to the other patients with RA or controls. High percentage of CD4+CD45RO+ T cells was also significantly associated with extraarticular manifestations. Patients with the sicca syndrome had significantly higher ratio of CD5+ B cells than patients without or with other types of extraarticular manifestations. CONCLUSION: Different disease manifestations in RA may be associated not only with certain RF isotypes and RF isotype combinations but also with changes in lymphocyte subsets in the blood. The relative increase of CD4+CD45RO+ T cells in the blood of IgA RF positive patients with RA might reflect preferential recruitment of CD8+CD45RO+ T cells to inflammatory sites.