Osteocalcin (OC) is a noncollagenous bone matrix protein containing gamma-carboxyglutamic acid, the synthesis of which is vitamin K dependent. Serum OC levels are generally believed to reflect the de novo synthesis of OC by osteoblasts and thus reflect bone formation. We measured serum OC levels by RIA in 48 patients receiving phenprocoumon anticoagulant treatment, which inhibits the posttranscriptional synthesis of gamma-carboxyglutamic acid, and in 22 matched normal subjects. The median serum OC level in the patients receiving phenprocoumon therapy was significantly lower than that in the normal subjects (P less than 0.0001). In 27 patients receiving anticoagulant therapy and in 21 normal subjects the proportion of noncarboxylated OC to total OC also was determined. The proportion of OC that was noncarboxylated was significantly higher in the patients receiving phenprocoumon therapy than in the normal subjects (P less than 0.0001). We conclude that OC carboxylation is impaired in patients receiving oral anticoagulant therapy. The decreased total OC levels in patients receiving phenprocoumon treatment might result from decreased bone formation, although these patients do not have symptoms of bone disease.