The objective of this study was to test the hypothesis of a diurnal fluctuation of circulating levels of endogenous tumor necrosis factor-alpha (TNF-alpha) in patients with colorectal cancer metastases. Serum levels of TNF-alpha were measured 6 times a day in 27 colorectal cancer patients as well as in healthy controls. The levels of TNF-alpha in serum from healthy controls were close to the detection limit of the method or were not detectable at all. Serum TNF-alpha levels in advanced cancer patients were substantially increased. Peak values appeared at 2 a.m. In contrast, the levels were low in the afternoon (2 p.m). The presence of a circadian rhythm was found with the acrophase at 0 hour 40 min.