In this investigation of B cells expressing the CD5 (Leu-1) cell surface marker, we found increased numbers of these cells in 13 of 19 patients with primary Sjögren's syndrome (SS) (68%), as well as in the rheumatoid arthritis patients. The percentage of B cells that demonstrated increased expression of CD5 was 46% in SS patients, 47% in rheumatoid arthritis patients, 24% in systemic lupus erythematosus patients, and 26% in normal subjects. Over a 2-year period, CD5 expression on B cells was a stable finding in several patients, except for 2 who required either steroid therapy or combined chemotherapy and irradiation for malignant lymphoma. Both of these patients had clinical remissions and their levels of CD5+ B cells returned to normal. The first patient had a clinical picture of SS/systemic lupus erythematosus overlap, associated with polyclonal B cell activation and decreased production of interleukin-2 in response to stimulation with phytohemagglutinin. These cellular immune abnormalities returned to normal after the institution of corticosteroids. Our observations suggest a relationship between the CD5+ B cell abnormality and disease activity. The results are discussed in relation to immunoregulatory properties of CD5+ B cells in autoimmune mice and the characteristic predisposition to malignant lymphoma among SS patients.