The factors that are responsible for trabecular bone loss in aging women are not completely understood. To evaluate declining renal function as a possible factor, we studied 19 Caucasian women (average age 67) who were from 6 to 41 years postmenopausal. Trabecular bone density was quantitated by computerized tomography of the spine. Serum calcium, phosphorus, and creatinine were normal in all subjects. Creatinine clearance averaged 74 ml/min (range 38-122), decreased with age (r = -0.60, P = 0.003), and was inversely related to serum creatinine (r = -0.51, P = 0.01). Bivariate regression demonstrated that bone density decreased with age (r = -0.59, P = 0.004); controlling for the effect of creatinine clearance weakened this correlation to r = -0.45 (P = 0.03); controlling additionally for 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) reduced the correlation coefficient to r = -0.34 (P = 0.11). Bone density also decreased in direct proportion to the decrement in creatinine clearance (r = 0.44, P = 0.03); controlling for the effects of 1,25(OH)2D and PTH reduced this correlation coefficient to r = 0.34 (P = 0.11). These results suggest that occult renal insufficiency may contribute to bone loss in aging women, and that this effect may be mediated in part by 1,25(OH)2D and PTH. In this age group renal function should be assessed by measuring creatinine clearance rather than the serum creatinine concentration since renal insufficiency can be masked by apparently normal circulating creatinine levels.