Bone metastases in cancer of the prostate are diagnosed routinely by isotope bone scintigraphy and the measurement of alkaline phosphatase in serum and the calcium excretion in urine. The specificity of these examinations is in general not satisfactory. We therefore investigated the diagnostic value of five new markers of bone formation and bone resorption for the detection of the metastatic process. In a group of 43 patients with carcinoma of the prostate the carboxyterminal propeptide, the carboxyterminal cross-linked telopeptide, the aminoterminal cross-linked telopeptide, and the deoxypyridinoline cross-links of type 1 collagen were measured as well as the specific bone alkaline phosphatase isoenzyme. A group of 34 patients with benign prostatic hyperplasia served as a control. A receiver-operating characteristic analysis was performed. It appeared that the sensitivity of carboxyterminal cross-linked telopeptide of type I collagen was the greatest (89%), while the best specificity was obtained for the deoxypyridinoline cross-links assay (92%). The diagnostic values of the new markers were generally comparable with those of alkaline phosphatase although carboxyterminal cross-linked telopeptide of type I collagen yielded better results, but those with carboxyterminal propeptide of type I procollagen were less satisfactory. Calcium excretion in urine had no added value at all.