It has been hypothesized that the pleasure of a reward in humans is mediated by an opioidergic system involving the hypothalamus, nucleus accumbens and the amygdala. Importantly, enjoying the pleasure of a reward is distinct from incentive salience induced by cues predicting the reward. We investigated this issue using a within subject, pharmacological challenge design with the opioid receptor antagonist naloxone and fMRI. Our data show that blocking opioid receptors reduced pleasure associated with viewing erotic pictures more than viewing symbols of reward such as money. This was paralleled by a reduction of activation in the ventral striatum, lateral orbitofrontal cortex, amygdala, hypothalamus and medial prefrontal cortex. Crucially, the naloxone induced activation decrease was observed at reward delivery, but not during reward anticipation, indicating that blocking opioid receptors decreases the pleasure of rewards in humans.