Osteoporosis is a frequent complication of rheumatoid arthritis (RA), especially in postmenopausal women, and may involve both juxtaarticular and generalized bone loss. To examine the effect of exogenous estrogens and endogenous androgens on bone loss in RA we determined rates of bone loss by serial bone density measurement for up to 4 years in 38 postmenopausal women with RA. Serum dehydroepiandosterone sulfate concentrations correlated significantly with the change in femoral neck bone but not in lumbar spine bone. Estrogen therapy prevented lumbar spine bone loss, but did not affect bone loss from the hip. These data suggest adrenal androgen status may influence bone loss in RA and that, although estrogen therapy can prevent bone loss from the spine, it may not prevent bone loss at sites near involved joints.