Serum Bone Gla Protein (BGP) levels were measured by both immunoradiometric assay (IRMA) and radioimmunoassay (RIA) to investigate the effect of intermittent 1,25(OH)2D3 administration to dialysis patients who could not tolerate an increase in an active vitamin D3 dose and/or calcium to control secondary hyperparathyroidism due to hypercalcemia. The administration of active vitamin D3 gradually increased the serum BGP to more than 3 times the original level by the 8th week. At the 12th week after starting the active vitamin D3 therapy, mean BGP was about twice the original level, which was about half the maximum level at the 8th week. The BGP (IRMA)/BGP (RIA) ratio was increased significantly at 4th and 8th weeks compared to the original level. During this period, serum calcium, phosphorous, or intact molecule PTH (I-PTH) levels showed insignificant changes, with a slight reduction in the mid molecule PTH (m-PTH) level, and a significant reduction in ALP. Serum BUN and creatinine levels were not changed significantly. These data suggest that BGP was increased through direct stimulation of osteoblasts by the active vitamin D3, and the increase was not due to deterioration of secondary hyperparathyroidism. The reduction of the increase in the BGP level at the 12th week with insignificant biochemical changes suggest that activation of osteoblasts by vitamin D3 may be transient. In conclusion, intermittent active vitamin D3 increases serum BGP, without deterioration of major biochemical changes even in patients with moderate to severe secondary hyperparathyroidism, although the increase may be transient. These facts suggest that the serum BGP of hemodialysis patients is controlled at least in part by active vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)