Mice are powerful models to investigate the genetic basis of food reward because many spontaneous obesity mutants exist and the murine genome is accessible to selectively targeted manipulations. Experiments in rats have shown that opioid receptor blockade reduces operant responding to food reinforcers. The present study investigated whether DBA/2J mice would display similar behavior in response to an opioid antagonist. Twelve male DBA/2J mice were trained to lever press for food reinforcers and subsequently randomized in a within subjects design for no injection, saline injection, or 10 mg/kg naloxone injection intraperitoneal (i.p.) 20 min before each daily trial under ad lib or food-deprived conditions. A significant main effect of injection occurred to reduce lever pressing by the mice. However, a greater pharmacological effect of naloxone occurred compared with saline on the operant responding only under the food-deprived conditions. Interestingly, the percentage of dispensed food pellets actually consumed was significantly reduced after naloxone injection compared with saline injection for either chow-based or sucrose pellets under ad lib or deprived feeding conditions. These data suggest that opioids specifically influence consumatory behavior in mice, but our findings on instrumental behavior were confounded by an independent inhibitory effect of an i.p. saline injection.