Dehydroepiandrosterone sulfate (DHEAS), testosterone, androstenedione, 17-beta estradiol and sex hormone binding globulin have been assayed in 50 HLA-identical postmenopausal rheumatoid arthritis (RA) discordant sibling pairs. The only difference was for DHEAS, siblings with RA having a significantly lower level than their sisters. However, in 68 patients with RA, the level of DHEAS inversely correlated with disease duration, a radiographic grading score, the Health Assessment Questionnaire score, duration of morning stiffness, and a clinical score of disease activity and severity (the Spread/Severity index). These observations, taken with that of previous work on DHEAS, suggest that low levels may be a consequence of RA rather than predisposing to the disease. The role of sex hormones in RA will have to be approached in alternative ways.