To investigate the stimulatory effect of vitamin D on biochemical markers of bone remodeling, 15 normal men (aged 26-45 years, mean 33.2) were treated orally with 1,25-dihydroxyvitamin D3, 2-mu-g daily for 7 days, and followed for a total of 16 weeks. Serum concentrations of 1,25-dihydroxyvitamin D3 rose 43% during the first week (p < 0.01), with no significant alteration in the level of 25-hydroxyvitamin D3. Serum level of immunoreactive parathyroid hormone (1-84) (iPTH) decreased markedly (p < 0.02), and the maximal renal reabsorption capacity of phosphate (TmP/GFR) increased (p < 0.05), both indicating the impact of the raised vitamin D level on target tissues. Serum phosphate and serum calcium increased during the treatment week (p < 0.05), as did the fasting renal excretion of phosphate and calcium (p < 0.01). However, a gradual fall in the excretion of hydroxyproline was seen in the observation period. The serum activity of acid phosphatase increased in the first weeks after vitamin D treatment, reaching significance at the end of week 2 (p < 0.05). Acid phosphatase activity was still increased at the end of the observation period (p < 0.02). These observations suggest a syncronization and recruitment of new bone resorptive cells. The immediate response to 1,25-dihydroxyvitamin D administration on the biochemical markers of formative bone cells was a marked increase in the serum level of osteocalcin (BGP), (p < 0.002) with a gradually fall during the next weeks. A secondary increase, however, was observed in the last two months of the follow-up period. Sixteen weeks after initiation of vitamin D treatment, BGP was still markedly increased (p < 0.01). Moreover, a gradual increase in bone alkaline phosphatase activity in serum was observed (p < 0.0001). It is concluded that short-term treatment with 1,25-dihydroxyvitamin D3 stimulates existing bone cells, and is capable of syncronizing and activating bone remodeling. However, activation of bone resorptive cells is not followed by increased bone resorption.