The physiological function of the peptide galanin (Gal) remains to be established. It is known to exist in high concentrations within the hypothalamus and to modulate the secretion of specific hormones, as well as to potentiate food consumption. Our study provides evidence for an essential function of neuronal Gal, within a specific hypothalamic area, in stimulating the behavioral process of fat ingestion and body weight gain. Through analyses of peptide levels via RIA and of gene expression via in situ hybridization, a close positive association is established between Gal in the paraventricular nucleus (PVN), particularly its midlateral region, and fat ingestion. No such relationship is detected for Gal in other brain areas or between PVN Gal and ingestion of carbohydrate or protein, supporting the behavioral and anatomical specificity of this relationship. Through PVN injection studies with antisense oligonucleotides to Gal mRNA, a dramatic decline in fat ingestion and body weight suggests that endogenous Gal contributes to the natural appetite for fat. Thus, Gal in the PVN is identified as a neurochemical marker for fat ingestion and, consequently, body weight gain.