Several reports have shown a defective Epstein-Barr virus (EBV)-specific suppressor T cell function in rheumatoid arthritis (RA), suggesting that EBV may have a role in the pathogenesis of RA. EBV-specific T cell regulation was studied in 47 EBV-immune RA patients and in 14 EBV-immune control subjects by comparing the secretion of IgM into supernatants of 28-day cultures of B cells alone and cocultures of B and autologous T cells. In control subjects, autologous T cells mediated a significant decrease in the secretion of IgM by B cells at 12 and 16 days of culture. Analysis of individual responses demonstrated the existence of 3 subgroups of RA patients: group I (18 patients) had a suppressor T cell function similar to that of controls; group II (21 patients) had a defective T cell function; group III (8 patients) was characterized by a "late help phenomenon." Moreover, in RA group III, IgM secretion in cultures of B cells alone was lower than that seen in controls, RA group I, or RA group II. Differences in the duration or severity of the disease, or in the use of slow-acting therapeutic agents, corticosteroids, and nonsteroidal antiinflammatory drugs could not account for these subdivisions. Thus, our study demonstrates that several immunoregulatory defects exist in subgroups of RA patients.