Accumulating evidence has implicated T cells in the pathogenesis of systemic lupus erythematosus (SLE). The CD69 antigen is an integral membrane protein rapidly induced on the surface of activated lymphocytes. We obtained CD4+ and CD8+ T cells from normal subjects and patients with SLE. The percentage of CD69 expression in freshly isolated cells and after in-vitro incubation with mitogens was quantified by three-colour immunofluorescent staining. Expression of this protein was increased in both CD4+ and CD8+ T-cell subsets from SLE patients when compared with normal cells, although the difference was significant only in the CD8+ T-cell subset (P = 0.05). Cellular activation increased CD69 expression. When stimulated with anti-CD2/CD2R or phytohaemagglutinin (PHA), the percentage and absolute numbers of CD69+ cells were lower in patients than in controls. Addition of anti-interleukin (IL)-10 monoclonal antibody (MoAb) increased the percentage of in-vitro CD69 expression in SLE cells. These results suggest that the peripheral blood lymphocytes from patients with SLE have an intrinsic defect that alters their activation process, including the expression of CD69, and might explain some of the T immunoregulatory abnormalities observed in these patients.