Sex steroids are believed to modulate the immune system in rheumatoid arthritis (RA). Since receptors for sex steroids are present on T-lymphocytes, which are thought to play a major role in the pathogenesis of RA, it is suggested that gonadal steroids can mediate their immunomodulating effect directly on T-lymphocytes. Recently a specific method for activating T-lymphocytes with immobilized anti-CD3 monoclonal antibodies was described. We investigated the influence of oestradiol, progesterone, testosterone and cortisol on lymphocytes stimulated by anti-CD3 mAb and PHA of postmenopausal women, comparing female patients with rheumatoid arthritis and age-matched control patients. The results show that oestradiol, progesterone and testosterone do not influence lymphocyte proliferation when stimulated with anti-CD3 mAb or phytohaemagglutinin (PHA). Cortisol, however, can suppress lymphocyte proliferation even at physiological concentrations in both patients with RA and controls. Inhibition of proliferation by cortisol is dose-related and has no significant correlation with RA disease activity. This inhibition differs individually and might explain the often variable response to corticosteroids in vivo.