Binge eating is often preceded by reports of negative affect, but the mechanism by which affect may lead to binge eating is unclear. This study evaluated the effect of negative affect on neural response to anticipation and receipt of palatable food in women with bulimia nervosa (BN) versus healthy controls. We also evaluated connectivity between the amygdala and reward-related brain regions. Females with and without BN (N = 26) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless solution. We measured negative affect just prior to the scan. Women with BN showed a positive correlation between negative affect and activity in the putamen, caudate, and pallidum during anticipated receipt of milkshake (versus tasteless solution). There were no significant relations between negative affect and receipt of milkshake. Connectivity analyses revealed a greater relation of amygdala activity to activation in the left putamen and insula during anticipated receipt of milkshake in the bulimia group relative to the control group. The opposite pattern was found for the taste of milkshake; the control group showed a greater relation of amygdala activity to activation in the left putamen and insula in response to milkshake receipt than the bulimia group. Results show that as negative affect increases, so does responsivity of reward regions to anticipated intake of palatable food, implying that negative affect may increase the reward value of food for individuals with bulimia nervosa or that negative affect has become a conditioned cue due to a history of binge eating in a negative mood.