The cause of anorexia associated with neoplasia is unknown, and some investigators have suggested a central mechanism. Recent neurophysiologic studies have revealed the possible role of serotoninergic system involving tryptophan (TRP) and its indole neurotransmitter metabolites in regulating particular aspects of feeding behavior. We therefore studied plasma and brain factors affecting TRP transport through the blood-brain barrier (plasma free and total TRP, albumin, nonesterified fatty acids, plasma neutral amino acids, brain uptake index [BUI] for TRP) and central serotonin metabolism (5-HT, 5-HIAA) in young, anorexic rats bearing the Walker-256 tumor injected intramuscularly. Plasma free TRP, but not plasma total TRP, and, more important, brain TRP and brain 5-HIAA were significantly higher in tumor-bearing rats than in pair-fed control animals. The results suggest an association between altered brain TRP metabolism and feeding behavior in tumor-related anorexia.