Levels of serum bone Gla-protein (BGP) were evaluated in 372 normal Japanese subjects (164 males, 208 females), ranging in age from 14 to 87 years, and in 194 patients with chronic renal failure, 181 of whom were on maintenance hemodialysis. The age-dependent serum BGP levels (mean +/- SD) determined by radioimmunoassay in normal subjects under 20 years old were 27.1 +/- 20.5 ng/ml, and 10.2 +/- 5.8 ng/ml in older subjects. Mean serum BGP increased significantly in patients with hemodialysis (35.1 +/- 24.3 ng/ml) and in patients with nonhemodialysis chronic renal failure (20.6 +/- 14.2 ng/ml). The mean BGP levels showed a trend toward higher values in the younger renal failure patients. However, the difference to the values of older patients did not reach a level of statistical significance. There was a significant (r = 0.84, p less than 0.001) positive correlation between serum BGP and serum creatinine for the nonhemodialysis group alone, but not for hemodialysis patients alone. A correlation was also observed between serum BGP and serum C-PTH in hemodialysis patients. Our results suggest that the serum BGP elevation in patients with chronic renal failure probably reflects not only decreased renal clearance but also increased bone formation.