BACKGROUND: The disturbances leading to cancer cachexia remain to be unraveled. Preliminary evidence suggests that arginine availability in cancer is reduced. However, no valid data are available on plasma arginine concentrations in cancer patients. OBJECTIVE: We aimed to determine whether there is evidence for disturbed arginine metabolism in cancer. DESIGN: We measured plasma arginine concentrations postabsorptively in patients with various types of tumors, hypothesizing that arginine concentrations would be lower than those in age- and sex-matched control subjects. Patients with localized tumors with a range of metabolic implications were studied: breast cancer (no weight loss), colonic cancer (sometimes weight loss), and pancreatic cancer (usually weight loss). Plasma amino acid concentrations were measured by HPLC. RESULTS: Plasma arginine concentrations were lower in patients with cancer (breast cancer: 80 +/- 3 compared with 103 +/- 9 micromol/L; colonic cancer: 80 +/- 3 compared with 96 +/- 7 micromol/L; pancreatic cancer: 76 +/- 5 compared with 99 +/- 7 micromol/L; P < 0.05 versus respective age- and sex-matched control subjects), irrespective of tumor type, weight loss, tumor stage, or body mass index (correlations with P > 0.05). CONCLUSIONS: Malignant tumors associated with various degrees of metabolic derangements are all associated with decreased plasma arginine concentrations, even without weight loss. This suggests that decreased arginine availability is a specific feature of the presence of cancer. These disturbances in arginine metabolism could contribute to the cascade of metabolic events leading to cancer cachexia.