Sex hormones have important effects on bone, especially in postmenopausal women. These hormones may be of particular significance in patients with rheumatoid arthritis (RA), who have a high frequency of osteoporosis. To examine this, we measured estrogen and androgen concentrations and bone mineral density (BMD) in 49 postmenopausal women with RA and 49 normal postmenopausal women. Compared with the controls, postmenopausal RA patients had significantly reduced levels of estrone (median 18 pmoles/liter versus 49; P less than 0.001), dehydroepiandosterone sulfate (DHEAS) (median 0.3 mumoles/liter versus 2.0; P less than 0.001), testosterone (median 0.6 nmoles/liter versus 0.95; P less than 0.001), and femoral BMD (mean 0.72 gm/cm2 versus 0.80; P less than 0.002). Prednisolone therapy in 22 patients (mean dosage 8 mg/day) was associated with reductions in estrone and testosterone levels; however, DHEAS and femoral BMD were also decreased in RA patients who were not receiving corticosteroids. Reduced DHEAS levels in postmenopausal women with RA may increase their risk of osteoporosis.