Rats were given imipramine or zimeldine orally for three weeks and the brain levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured. The concentration of NPY-LI in frontal cortical tissue was elevated by 40 and 60%, respectively. Imipramine increased the concentration of NPY-LI in the hypothalamus by 65% while zimeldine was without effect. The concentration of NPY-LI in the parietal cortex was unaffected by either of the drugs. These observations support the hypothesis that NPY might be involved in the pathophysiology of depressive illness.