Following surgical ligation of the middle cerebral artery in the rat, central catecholamine containing neurons were studied using the glyoxylic acid histochemical technique. By 5 days after the ischemic lesion, the density of fluorescent varicosities decreased in both uninjured cerebral cortex and the cerebellar cortex and the intensity of fluorescence of somata in the ipsilateral and contralateral locus coeruleus decreased as compared with controls. At 20 days afer lesioning, catecholamine containing neurons looked normal under fluorescence microscopic examination, except fine varicose fluorescent axons were present for the first time among the cellular debris of the lesion and appeared to have sprouted into the lesion site. However, by 40 days after surgery, there was a marked increase in the density of fluorescent varicosities in the uninjured ipsilateral cerebral cortex, in the contralateral cerebral cortex, and in the cerebellum. These observations confirm the view that an ischemic cortical lesion can lead to profound changes in cetecholamine containing neurons in distant areas of the brain which are uninjured by the local infarction.