Synovial and peripheral blood T cells from patients with rheumatoid arthritis are functionally deficient. This may be secondary to their reduced cytokine (e.g. interleukin‐2) synthesis. We have investigated the possibility of an alteration in pathways common to interleukin‐2 production and proliferation in peripheral blood T cells from patients with active rheumatoid arthritis. Intracellular calcium levels ([Ca²⁺]_i) were analyzed by flow cytometric methods in Indo 1‐loaded T cells. These were purified by negative selection from patients or age/sex‐matched controls, and stimulated with phytohemagglutinin‐P or anti‐CD3. Rheumatoid [Ca²⁺]_i responses to both stimuli were reduced (p < 0.005). Patient cell samples included a larger proportion of non‐responding cells, but even in the responsive population the magnitude of the response in rheumatoid cells was impaired compared with those in normal cell samples (p < 0.0001) for both stimuli. Proliferation responses were also impaired (p < 0.005), and there was a positive correlation between the paired [Ca²⁺]_i elevation and proliferative responses for both stimuli. CD2 and CD3 expression were normal, and the proportions of CD4, CD8 and CD45RO and CD45RA subsets were also unaffected by disease. Thus a signaling defect downstream of CD2 or CD3 surface molecules may contribute to functional deficiencies in rheumatoid T lymphocytes. This effect is not due to non‐steroidal anti‐inflammatory drugs which some patients were taking. We have demonstrated similar alterations in [Ca²⁺]_i responses and proliferation in a smaller study of patients with inflammatory bowel disease, indicating that such changes might be present in other chronic inflammatory states.