BACKGROUND The syndrome of cancer cachexia can have a significant impact on response to therapy as well as on survival in cancer patients. Therapies directed at metabolic perturbations in cachectic patients are dependent on nutritional repletion and maintenance of adequate amino acid substrate levels. This study compares the ability of oral feeding, enteral nutrition, and total parenteral nutrition to alter plasma amino acid levels in cancer patients. METHODS Patients with esophageal cancer were stratified by weight loss. Patients with < 20% weight loss were randomized to continue an ad libitum oral diet (group I) or to receive total parenteral nutrition (group II) for 2 weeks; patients with > 20% weight loss were randomized to receive either enteral nutrition (group III) or total parenteral nutrition (group IV) for 2 weeks. Plasma amino acid levels were measured before the study and again after 2 weeks of nutrition support. RESULTS Before therapy, there was no difference between the groups in total or essential amino acid levels; however, patients in all groups had significantly lower total amino acid levels compared with those of normal controls. After 2 weeks of treatment, patients in group I and III showed no difference in individual, essential, or total amino acid levels. However, patients in groups II and IV showed significant increases in a number of individual amino acids as well as in essential and total amino acid levels after 2 weeks of TPN. CONCLUSIONS Patients with esophageal cancer demonstrated significant alterations in amino acid profiles compared with those of normal controls. Total parenteral nutrition was superior to ad libitum oral feeding and jejunostomy feeding in repleting plasma amino acid levels.