To determine the relationship between the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and those of bone formation and resorption markers in prostate cancer patients, we measured the serum levels of the cytokines and examined their relationship to biochemical markers of bone turnover in 46 untreated patients with prostate cancer. The carboxy-terminal propeptide of type I procollagen (PICP) levels were used as a parameter of bone formation, and the carboxy-terminal telopeptide of type I collagen (ICTP) levels were used as a marker of bone resorption. The relationship of these markers to the degree of bone metastasis was also examined. The serum levels of IL-6, PICP, ICTP, and prostate-specific antigen (PSA) were significantly higher in the patients with prostate cancer with bone metastasis (n = 23) than in the patients without bone metastasis (n = 23). The serum levels of TNF-alpha in approximately 85% of the patients were under the detectable limit (5 pg/ml). The serum levels of IL-6 were not correlated with those of PICP or ICTP, but were related to the extent of bone metastasis. These results indicate that among patients with prostate cancer, IL-6 and TNF-alpha may not play major roles in the increased bone resorption in the patients with metastatic spread to bone. Our study thus demonstrated that the serum levels of IL-6 are closely related to the metastatic burden to osseous tissue in prostate cancer patients.