The present study was undertaken to evaluate the relationship between serum tumor necrosis factor (TNF) and cachexia in patients with prostate cancer. TNF levels were determined in 110 serum samples from prostate cancer patients by an enzyme immunoassay. Serum TNF activity was positive in 76% of the patients with relapsed disease, whereas only 11% of the untreated patients and 0% of the patients in remission as a result of endocrine therapy were positive. The serum total protein and albumin levels, hemoglobin levels, and body mass index of the patients with elevated serum TNF levels were significantly lower (P < 0.05) than the corresponding values in patients with undetectable serum TNF levels. The serum TNF levels of patients with serum albumin levels of <3.5 g/dl, serum total protein levels of <7.0 g/dl, hemoglobin levels of <11.0 g/dl, and a body mass index of <21 kg/m2 were significantly higher (P < 0.05) than the values in their respective counterparts. There was a significant correlation between the detectability of serum TNF and performance status (P < 0.05). Patients with elevated serum TNF levels had a significantly higher mortality rate (P < 0.05) than those with undetectable serum TNF levels. These findings suggest that TNF may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer.