The present study examined the interrelationships between feeding responses produced by μ opioid receptor agonists and melanocortin-3 or 4 (MC-3/4) receptor antagonists. Feeding induced by the μ-sensitive opioid peptide, β-endorphin (βEND, 10 μg, icv) was significantly and dose-dependently reduced by pretreatment with the MC-3/4 receptor agonist, melanotan-II (MTII: 0.01–10 nmol, icv). Moreover, the selective μ opioid antagonist, β-funaltrexamine (βFNA: 2–20 μg, icv), significantly and dose-dependently reduced feeding and weight gain elicited by the potent MC-3/4 receptor antagonist, SHU-9119 (0.5 nmol, icv), especially at those intake periods (24–48 h) when SHU-9119 produced maximal ingestive effects. These data extend previous findings demonstrating interactions between opioid and melanocortin receptors in the mediation of food intake.