Capsaicin, one of the pungent principles of hot pepper, has been reported to cause a cessation of increases in body weight and fat gain induced by high-fat feeding. Especially, in body weight and feeding control, cholecystokinin (CCK) has been well known as a satiety signal and neuropeptide Y (NPY) has been described as one of the most potent orexigenic signals. This study was carried out to investigate the effect of capsaicin on CCK- and NPY- immunoreactivities (IR) in the brain of high-fat fed rats. The animals were divided into normal-fat diet (NF), high-fat diet (HF) and high-fat diet containing capsaicin (HF-CAP) groups. Mean body weight gain (MBWG) of HF group was higher than that of NF group. However, in HF-CAP group, MBWG was lower than that of HF group. CCK-IR in suprachiasmatic nucleus (SCN), paraventricular nucleus (PVN), median eminence (ME), arcuate nucleus (ARC) and amygdala was not prominent in all the groups. In cerebral cortex, CCK-IR was more reduced in HF-CAP group than in the other groups. In the HF-CAP group, NPY-IR in the hypothalamic nuclei, amygdala and cerebral cortex was more poorly found than in the NF and HF groups. It is concluded that (1) NPY-IR may react more sensitively on capsaicin than CCK-IR, (2) no rapid increase of body weight in capsaicin treated rats may result from the diminished food intake through the low expression of NPY in hypothalamus in HF-CAP group.