AbstractThe appetite‐stimulating (orexigenic) potential of the peripheral dopamine (DA) receptor antagonist domperidone was compared with that of the central DA antagonist pimozide in anorexic, tumor‐bearing rats. DA antagonists were administered via the intraperitoneal route on Days 7–15 after the subcutaneous implantation of the Walker 256 carcinosarcoma. The doses of domperidone injected were 0.05 and 0.1 mg/kg once daily and 0.1 mg/kg twice daily. The dose of pimozide given was 0.1 mg/kg daily. While all doses of DA antagonists caused an initial drop in body weight and food intake, the body weight of pimozide‐injected animals was not reduced significantly (in the early stages of drug treatment) as it was with the various doses of domperidone. There was significantly more food in the stomachs of domperidone‐and pimozide‐treated animals compared with those of the vehicle‐treated, tumor‐bearing animals at the time of sacrifice. These results indicate that short‐and long‐term satiety factors, in addition to gastric motility, should be considered when assessing the orexigenic potential of various drugs.