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An increased level of apoptotic material and B cell activation leading to autoantibody production are hallmarks of systemic lupus erythematoses (SLE). Increased FAS expression, apoptosis, and CD154-mediated signaling, enabling T-B cell interaction are involved in the pathogenesis of SLE. This study addresses the expression profile of CD154 and FAS in the peripheral blood of patients with SLE, rheumatoid arthritis (RA) and normal healthy control donors. Surface markers on peripheral blood T and B cells from patients and healthy control donors were assessed using flow cytometry. The expression of CD154 and FAS were significantly increased in T and B cells of SLE patients as compared to healthy control donors and RA patients. In SLE and RA patients, FAS expression strongly correlated with CD154 expression on T cells, which was not found in healthy control donors. FAS expression was also associated with the occurrence of anti-DNA antibodies. We demonstrate high CD154 and FAS expression as a characteristic feature of SLE. This pattern may reflect simultaneous activation of apoptosis and activation of B-T cell interaction in SLE.