Cancer cachexia may be mediated by endogenous peptides such as tumour necrosis factor alpha (TNF-α). Insulin resistance occurs in these patients, and is also seen experimentally with TNF-α administration. In this study, insulin sensitivity and energy metabolism were measured in 11 patients with gastrointestinal cancer and ten controls, using the euglycaemic glucose clamp and indirect calorimetry. Patients with cancer were significantly more insulin resistant than controls (P < 0.01) and in such patients insulin resistance correlated with serum TNF-α level (rs = 0.74, P < 0.01). Fasting insulin levels also correlated inversely with insulin sensitivity (rs = −0.62, P = 0.003). These results suggest a possible association between endogenous TNF-α production and insulin resistance in patients with gastrointestinal cancer.