Systemic lupus erythematosus ( SLE) is characterized by loss of immune tolerance. A hallmark of SLE is the presence of autoantibodies resulting from B cell hyperactivity. Previous studies have shown that the presence of abnormal B cell subsets in the periphery, such as CD27(high)CD20(-) B cells, correlate with disease activity. We examined the relationship between the expression of CD70, the ligand for CD27 expressed by activated T cells, and indicators of disease activity. A significant increase in median CD70(+)CD4(+) T cell frequencies and memory CD45RA(-)CD4(+) T cell frequencies was observed in SLE samples as compared to healthy controls. The frequencies of CD70(+)CD4(+) T cells correlated with disease duration but not age, treatment, or disease activity. Although a majority of CD70(+)CD4(+) T cells appeared to be effector memory cells, mitogen- stimulated CD70(+)CD4(+) T cells were capable of secreting a full repertoire of effector cytokines. Despite the presence of activated CD4(+) T cells, no increase in immunosenescent CD4(+) T cells, as defined by the loss of CD28 and/ or the acquisition of CD57 was observed in samples from SLE patients. These studies indicate that increased CD70 expression might serve as a useful marker of abnormal T cell activity in SLE.