Interleukin 2 (IL-2) production and proliferative responses of peripheral blood mononuclear cells (PBMC) stimulated with three concentrations of PHA were measured in 75 patients with rheumatoid arthritis (RA) and 25 normal controls. All patients were on a standard therapeutic regime, and were assessed for disease activity by clinical and laboratory criteria. Rheumatoid cells showed significantly lower IL-2 production and proliferation than normal PBMC at all PHA doses. These differences were not attributable to different kinetics. Within the rheumatoid population, both IL-2 levels and proliferation were lower in patients with active disease than those with inactive RA. Patients with extra-articular disease showed the most pronounced defects. Proliferative responses showed an inverse correlation with clinical indices of disease activity but not with measures of the acute phase response. Rheumatoid patients had higher proportions of CD4+, TFR+ and Tac+ lymphocytes than controls. Both proliferative responses and IL2- levels showed a positive relationship with the proportion of CD4+ cells, and an inverse relationship with Tac+ lymphocytes. Monocyte depletion and partial reconstitution resulted in an increase of both proliferation and IL-2 production, which was more marked in RA patients, suggesting that depressed IL-2 production may relate in part to monocyte effects. However, this cannot completely explain the magnitude of the defects observed, because normal monocytes did not increase the responses of rheumatoid lymphocytes, neither did rheumatoid monocytes suppress the responses of normal lymphocytes.