In 27 patients undergoing arthroscopy of the knee for treatment of meniscal diseases, biochemical markers of bone metabolism were measured in cancellous bone, and levels were compared with concentrations obtained from peripheral blood. Bone-specific alkaline phosphatase, osteocalcin, and collagen Type I metabolites (procollagen Type I N-terminal peptide and carboxy-terminal cross-linked telopeptide) were studied simultaneously in serum and in the distal femur using a radioimmunoassay. Although levels of bone-specific alkaline phosphatase and osteocalcin did not differ between serum and cancellous bone, concentrations of collagen Type I metabolites were elevated significantly in healthy cancellous bone. The close correlations between bone and serum concentrations confirmed accuracy of results obtained from cancellous bone. The mean bone-to-serum ratio for alkaline phosphatase and osteocalcin was 1.1 and 1.2, respectively. Collagen Type I metabolite ratios of 2.2 (for carboxy-terminal cross-linked telopeptide) and 2.3 (for procollagen Type I N-terminal peptide) indicate that these markers are formed locally and then released into the circulation. Bone seems to be a major contributor of collagen Type I metabolites to the serum pool.