Urinary concentration of pyridinoline and deoxypyridinoline, novel markers of bone resorption, was measured serially in patients with prostate cancer as markers of metastatic bone tumor. In 11 patients, five without bone metastasis and six with bone metastasis, pyridinoline and deoxypyridinoline were serially monitored for between 6 and 24 months. All patients received some hormonal therapy with or without radical prostatectomy. Pyridinoline and deoxypyridinoline were measured by ion-paired high-performance liquid chromatography and were adjusted according to urinary creatinine concentration. The sequential changes of pyridinoline and deoxypyridinoline were compared with those of prostatic specific antigen and alkaline phosphatase as well as with the findings of bone scintigrams. During the observation periods, no metastatic bone lesion developed and no significant changes in pyridinoline and deoxypyridinoline occurred in the five patients without bone metastasis. In the six patients with bone metastasis, the levels of prostatic-specific antigen showed relatively rapid decreases after starting therapy. In contrast, the levels of pyridinoline, deoxypyridinoline and alkaline phosphatase showed transient increases followed by gradual decreases in most cases. Correlations were observed between the changes of pyridinoline and deoxypyridinoline and the findings of bone scintigrams. The data suggest that serial monitoring of pyridinoline and deoxypyridinoline could be clinically useful as markers of metastatic bone tumors and may allow less frequent bone scintigrams during patient followup.