This study was designed to test the hypothesis that a short treatment course of 1,25(OH)2D3 elicits a stimulation of osteoblast activity without any action on the osteoclast. To test this, oral daily doses of 0.5 microgram or 1 microgram of 1,25(OH)2D3 were administered for 7 days to two groups (n = 5 and n = 7, respectively) of postmenopausal women with low bone mineral density. Markers of osteoblast activity, i.e. osteocalcin (BGP), total alkaline phosphatase activity (ALP) and bone alkaline phosphatase activity (BALP), and markers of osteoclast activity, i.e. hydroxylysyl-pyridinoline (Pyr), lysyl-pyridinoline (D-Pyr), and galactosyl-hydroxylysine (GHyl) were measured in plasma and in fasting urinary samples, respectively, at sequential times during and after 1,25(OH)2D3 administration. It resulted that short term 1 microgram 1,25(OH)2D3 oral administration induced a significant (P < 0.05) rise of BGP serum level without any associated increase of D-Pyr and GHyl, the latter also expressed as GHyl to GGHyl ratio. Urinary Pyr increased significantly after 1 microgram daily doses of 1,25(OH)2D3. Thus, a short course of 1 microgram daily doses of 1,25(OH)2D3 elicits a stimulation of osteoblast activity without any enhancement of D-Pyr, the most specific marker of osteoclast activity. The enhancement of Pyr after 1 microgram daily doses of 1,25(OH)2D3 might be due to the activation of extraosseous metabolic pathways rather than to the activation of osteoclast.