Because defective bone mineralization occurs in hypophosphatasia (HP) and the source of bone alkaline phosphatase is the osteoblast, we investigated another marker of osteoblast activity, namely the production of osteocalcin in an HP family and controls. The mean basal osteocalcin levels in the two affected young adults and their parents (the apparent heterozygotes) were 3.4 ng/ml (range 2.5-4.6) and were not different from the levels in age- and sex-matched controls (3.6 ng/ml; range 2.5-4.6). Furthermore, the ratio of carboxylated to total osteocalcin was normal. The rise in osteocalcin after 1,25-dihydroxycholecalciferol stimulation (2 micrograms daily for one week) was slightly greater in the controls than in the HP family. These results support the concept that there is no global defect in osteoblast function in this family with HP.