Many malnourished patients with cancer fail to gain weight with what appears to be adequate nutritional support. Metabolic abnormalities resulting from remote effects of the tumor on host metabolism have been postulated to increase energy requirements in such cancer patients. In the current study, 44 patients with lung cancer who had significant weight loss (16 +/- 2% of usual body weight) were studied under metabolic ward conditions. Whole body glucose production rates were significantly elevated in cancer patients compared to age-matched healthy controls. Blood glucose levels 2 hours after a standard oral glucose challenge were also significantly increased, but insulin levels were not different at this time. Fasting glucose and insulin levels were not different. Fasting plasma alanine levels were significantly decreased in these patients, while branched-chain amino acids were not different. Increased alanine flux for gluconeogenesis is likely to reflect a basic metabolic abnormality in patients with cancer and could be explained on the basis of a resistance to insulin action in such patients.