Nutritional state (e.g. fasted vs. fed) and different food stimuli (e.g. high-calorie vs. low-calorie, or appetizing vs. bland foods) are both recognized to change activity in brain reward systems. Using functional magnetic resonance imaging, we have studied the interaction between nutritional state and different food stimuli on brain food reward systems. We examined how blood oxygen level-dependent activity within a priori regions of interest varied while viewing pictures of high-calorie and low-calorie foods. Pictures of non-food household objects were included as control stimuli. During scanning, subjects rated the appeal of each picture. Twenty non-obese healthy adults [body mass index 22.1 ± 0.5 kg/m2 (mean ± SEM), age range 19–35 years, 10 male] were scanned on two separate mornings between 11:00 and 12:00 h, once after eating a filling breakfast (‘fed’: 1.6 ± 0.1 h since breakfast), and once after an overnight fast but skipping breakfast (‘fasted’: 15.9 ± 0.3 h since supper) in a randomized cross-over design. Fasting selectively increased activation to pictures of high-calorie over low-calorie foods in the ventral striatum, amygdala, anterior insula, and medial and lateral orbitofrontal cortex (OFC). Furthermore, fasting enhanced the subjective appeal of high-calorie more than low-calorie foods, and the change in appeal bias towards high-calorie foods was positively correlated with medial and lateral OFC activation. These results demonstrate an interaction between homeostatic and hedonic aspects of feeding behaviour, with fasting biasing brain reward systems towards high-calorie foods.