6-hydroxydopamine (6-OHDA), a catecholamine neurotoxin, has been shown previously to induce degenerative changes in nerve terminals innervating proopiomelanocortin (POMC) cells of the pituitary intermediate lobe. The present study provides evidence for regeneration of nerve fibers to the pituitary within 4 weeks of drug treatment. Adult male Sprague-Dawley rats were treated with 6-hydroxydopamine (150 mg/kg) on Days 1 and 3 and then perfused for light or electron microscopy (EM) of the pituitary intermediate lobes at 1, 2, 3, or 4 weeks after the first injection. At 1, 2, and 3 weeks after drug treatment, the number of normal-appearing nerve terminals was significantly lower than that in controls, while at 4 weeks after 6-OHDA, the number of normal nerve terminals did not differ significantly from that of control rats. Tyrosine hydroxylase-immunoreactive fibers appeared more intensely stained at 1 and 2 weeks after 6-OHDA treatment, suggesting continued and perhaps enhanced synthesis of the enzyme by hypothalamic cell bodies to the remaining terminals. Serotonin immunoreactivity after 5-hydroxytryptophan pretreatment was not detectable at 1 week after drug treatment, but was clearly visible in fibers innervating the intermediate lobe at 3 weeks, indicating a return of uptake ability and conversion of the precursor to serotonin by the regenerating terminals. Chemical denervation of the intermediate lobe followed by regeneration of nerve fibers will be useful for examination of regulatory mechanisms for the POMC secretory cells.