Serum bone Gla protein (BGP) concentrations were measured in 24 hyperthyroid patients before and after treatment. Before treatment, the mean concentration was higher [11.8 +/- 3.4 ( +/- SD) ng/ml] in the patient group than in a group of 12 age-matched normal subjects (6.1 +/- 1.7 ng/ml; P less than 0.001); 16 of the 24 patients had a value above the normal range. Serum BGP concentrations in the patients correlated significantly with serum T3 (r = 0.65; P less than 0.001) and T4 concentrations (r = 0.56; P less than 0.01). Other biochemical markers of bone metabolism (serum alkaline phosphatase, serum and urinary calcium, and urinary hydroxyproline) did not correlate with circulating thyroid hormone levels. Serum BGP also was measured after the patients had become euthyroid; 23 measurements were made on 16 patients at various times after the start of treatment. All values were normal after 16 weeks; before this period, most of the values were still above the normal range despite normal plasma thyroid hormone concentrations in all patients. These results suggest that BGP is a sensitive marker of bone metabolism alterations during hyperthyroidism.