Numerous studies have demonstrated that consuming high-calorie food leads to subsequent overeating by chronic dieters. The present study investigates the neural correlates of such self-regulatory failures using fMRI. Chronic dieters ( n = 50) and non-dieters ( n = 50) consumed either a 15-oz glass of cold water or a 15-oz milkshake and were subsequently imaged while viewing pictures of animals, environmental scenes, people, and appetizing food items. Results revealed a functional dissociation in nucleus accumbens and amygdala activity that paralleled well-established behavioral patterns of eating observed in dieters and non-dieters. Whereas non-dieters showed the greatest nucleus accumbens activity in response to food items after water consumption, dieters showed the greatest activity after consuming the milkshake. Activity in the left amygdala demonstrated the reverse interaction. Considered together with previously reported behavioral findings, the present results offer a suggested neural substrate for diet failure.