β-Chlornaltrexamine (β-CNA) is a non-equilibrium opioid receptor antagonist which alkylates and inactivates opioid receptors. Because opioid peptides are thought to contribute to the regulation of food intake, we examined the effects of intracerebroventricular (icv) injections of β-CNA on the food intake and body weight of male rats. We also tested the ability of β-CNA to block food intake stimulated by selective agonists of kappa, mu and delta opioid receptors: dynorphin A (DYN), Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO), and [(D-Ser2, Leu5]-enkephalin-Thr6 (DSLET). Treatment with β-CNA caused a long-term (2-4 days) reduction in daily food intake and a concomitant reduction in body weight. An additional experiment indicated that the weight loss after β-CNA treatment could be completely accounted for by the reduction in intake. β-CNA treatment also abolished or greatly attenuated the feeding effects of DAGO, DSLET and DYN, even when these peptides were tested 26 hours after β-CNA administration. The long duration of the effects of β-CNA suggests that this compound will be a useful pharmacological tool in further study of the opioid feeding system.