We studied the expression and function of 2 cell surface markers that induce T cell activation, CD3 and CD5, in 19 patients with primary Sjogren's syndrome (SS). The expression of CD3+ lymphocytes was normal, but CD3 function was moderately reduced, as measured by anti-CD3-induced T cell proliferation. Anti-CD3-induced stimulation of T cell help for Ig production and non-major histocompatibility complex-restricted (natural) killing were normal. In contrast, there was reduced expression and function of the CD5 molecule on peripheral blood lymphocytes of the SS patients. The ratio of CD5+ to CD3+ lymphocytes was 0.45 in SS patients compared with 0.85 in normal subjects, indicating that the CD3+ cells are relatively CD5-deficient in SS patients. Anti-CD5 monoclonal antibody did not augment suboptimal anti-CD3 stimulation of whole peripheral blood lymphocytes or of purified T lymphocytes from SS patients, which indicated impaired functioning of the CD5 molecule. A significant impairment in proliferation was found in response to phorbol myristate acetate and to ionomycin in combination, suggesting