Previous studies have indicated that food deprivation exerts various effects on brain neurotransmitters and that mild stress causes a selective enhancement of dopamine activity in the rat medial prefrontal cortex. In the present study it was found that in rats 24 h of food deprivation produced an increase in levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the medial prefrontal cortex but not in the nucleus accumbens or caudate-putamen. This selective increase in mesocortical dopamine activity is comparable to that found with mild footshock stress exposure and indicates that food deprivation may function as a stressor.