We measured neuropeptide Y (NPY) concentration in microdissected hypothalamic nuclei, by radioimmunoassay, and NPY mRNA in the hypothalamus in rats treated systemically with the nonspecific opioid antagonist, naloxone, to produce mild anorexia. Twenty rats were treated with daily SC injections of naloxone (7.5 mg/kg); 20 were treated with vehicle alone. Naloxone produced a 7% reduction in food intake (p < 0.01) and a reduction in weight gain (p < 0.002). Neuropeptide Y concentrations were increased specifically in the dorsomedial nucleus of the hypothalamus (DMN) in rats treated with naloxone (6.8 +/- 0.7 fmol/micrograms protein vs. 3.1 +/- 1.0 fmol/micrograms protein, p < 0.05, n = 10 per group). Total hypothalamic NPY mRNA was unchanged. Neuropeptide Y-opioid interactions may be important in the control of food intake.