Previous studies have shown that the regulation of hunger and satiety is accompanied by coordinate changes in cortical excitability. Starved subjects show a transient negative shift in the scalp-recorded cortical direct current (DC-)potential in the beginning of eating, indicating increased cortical excitability. With increasing satiety, the DC negativity becomes soon replaced by a reward related positive potential shift. Neuropeptide Y (NPY) is known from animal studies to increase food intake and induce weight gain, which might result from increasing hunger drive or reducing satiety. Here we investigated whether NPY affects the cortical sequelae of hunger and satiety regulation as reflected by cortical DC-potentials in man. DC-potentials were recorded over frontal (Fz, F3, F4), central (Cz, C3, C4) and parietal (Pz, P3, P4) electrode positions in 14 subjects who had abstained from eating for 15 h and who were intranasally administered 50 nmol of NPY and placebo 20 min prior to recordings. After a 3-min baseline epoch, subjects consumed 400 ml of liquid food within 5 min. Recordings ended 7 min after food consumption. In the placebo condition during food intake, with some delay a positive DC-potential shift developed which was most pronounced over frontal and central areas and reached maximum values 0-3 min after food consumption. NPY reduced this satiation associated positive shift (p<0.05) over all areas except P3 and Pz. Data suggest that NPY exerts its orexigenic influence by attenuating mechanisms of satiation.