We have reported that abnormal lymphocyte function in Sjogren's syndrome occurs almost exclusively in patients with HLA-B8. We now report that most clinically normal individuals with this antigen have a similar impairment of cellular immunity. This finding suggests that the lymphocyte abnormality in Sjogren's syndrome is not secondary to the disease process or medication and might have primary etiological significance. The lymphocyte abnormality is expressed as a decreased proliferative response to suboptimally stimulating concentrations of phytohemagglutinin (PHA) and concanavalin A (Con A). In contrast, the response to optimally stimulating concentrations of PHA and Con A is unaffected. The imparied mitogen responsiveness appears to be intrinsic to the T lymphocytes, as it can be demonstrated in purified T cell preparations.