To evaluate the effects of the short-term, high-dose sodium heparin therapy on biochemical markers of bone metabolism, we studied 20 patients (11 males and 9 females) with pulmonary embolism, treated with sodium heparin (daily dose range: 40,000-45,000 I.U. by continuous i.v. infusion). Heparin therapy lasted 5-7 days, after which patients received warfarin over 12 months. Eleven patients (6 males and 5 females) with ischaemic stroke, treated with i.v. glycerol and pentoxifilline, were used as controls. Before and after therapy serum and urinary markers of bone metabolism were evaluated; in 12 heparin-treated pts., the parameters were also evaluated 4 months after discontinuation of warfarin therapy. After heparin therapy a significant reduction vs. basal value was observed in levels of serum osteocalcin (ng/ml;mean + SEM): 3.32 & 0.19 vs. 2.05 + 0.21; p < 0.001. In the 12 patients evaluated 4 months after discontinuation of warfarin therapy, serum osteocalcin levels returned to basal value: 3.41 + 0.12 ng/ml (p:n.s.). No significant changes of the examined parameters were observed in controls. In conclusion, our data seem to indicate an effect of i.v. short-term heparin therapy on bone metabolism. This effect seems to be characterized by an inhibition of osteoblast function as suggested by the reduction of serum osteocalcin levels.