We investigated whether, in rheumatoid arthritis (RA), the CD45 isoform expression of peripheral blood T-lymphocytes (T-PBL) is related to auto-immune processes (e.g. IgM rheumatoid factors) and to clinical manifestations. By three-colour flow cytometry, we quantified three subsets of CD4+ or CD8+ T-PBL: “naive” CD45RA+,RO−, “transient” CD45RA+,RO+, and “memory” CD45RA−,RO+ cells, in 102 patients with RA and in 41 age- and sex-matched controls. The serum levels of rheumatoid factors (RF) were determined — besides conventional agglutination tests — by ELISA (IgM-RF). Extensive clinical examination was performed at the time of blood sampling. In RA, age, sex and drug therapy did not constitute major influences on the CD45RA/RO patterns. In “healthy” men, higher age significantly correlated with fewer naive and more memory CD4+ T-PBL (P<0.01). In RA, distinct correlations between the T-PBL subsets, autoimmune and clinical manifestations became obvious when patients with low and high levels of RF against human IgG Fc fragments, as determined by ELISA, were analysed separately. RA patients with high IgM-RF had elevated proportions of CD45RO+ T-PBL (P<0.05), that correlated with clinical parameters of disease activity (tender joint count, Ritchie index, P<0.05) and outcome (Health Assessment Questionnaire, Larsen radiographic scores, P<0.05). The proportions of memory CD4+ and CD8+ T-PBL correlated strongly (P<0.001) with the IgM-RF levels. Within 1 year, only three of 34 patients (disease duration of 5–9 years) showed seroconversion from low to high levels of IgM-RF (and positive agglutination tests); this was paralleled by reductions in naive and increases in transient T-PBL (P<0.02). Thus, in RA, the proportions of memory CD4+ and CD8+ T-PBL correlate with the level of IgM-RF and, together with transient T-PBL, with clinical parameters of disease activity and outcome.