Serum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 microgram/day of 1,25-dihydroxyvitamin D3(1,25(OH)2D3). Basal serum BGP was significantly lower in osteoporotic women (3.8 +/- 1.4 ng/ml) than in age-matched controls (6.8 +/- 2.0 ng/ml). During 1,25(OH)2D3 therapy serum BGP increased so that the mean of the values observed on treatment (4.8 +/- 1.5) was significantly higher than the mean basal value. It is known that BGP synthesis is stimulated by 1,25(OH)2D3 and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)2D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)2D3 treatment was a consequence of osteoblast stimulation.