We have previously suggested that during or prior to activation of anticipatory behaviour to a coming reward, mu-opioid receptors are activated. To test this hypothesis schedule induced food-anticipatory activity in mu-opioid receptor knockout mice was measured using running wheels. We hypothesized that mu-knockout mice show little food-anticipatory activity. In wildtype mice we observed that food-anticipatory activity increased proportional to reduced food intake levels during daily scheduled food access, and thus reflects the animal's physiological need for food. mu-Knockout mice do not adjust their schedule induced running wheel behaviour prior to and during feeding time in the same way as wildtype mice; rather than showing more running wheel activity before than during feeding, they showed an equal amount of activity before and during feeding. As food-anticipatory activity is dependent on the mesolimbic dopamine system and mu-opioid receptors regulate dopaminergic activity, these data suggest a change in the dopamine system's activity in mu-knockout mice. As we observed that mu-knockout mice tended to show a stronger locomotor activity response than wildtype mice to the indirect dopamine agonist d-amphetamine, it appears that the dopaminergic system per se is intact and sensitive to activation. We found no differences in the expression of pro-opiomelanocortin, a precursor of endogenous endorphin, in the arcuate nucleus between mu-knockout mice and wildtype mice during restricted feeding, showing that the mu-opioid receptor does not regulate endogenous endorphin levels. These data overall suggest a role for mu-opioid receptors in adapting reward related behaviour to the requirements of the environment.