The effects of immobilization stress on the activity of the adrenaline-forming enzyme, phenylethanolamine N-methyltransferase (PNMT), have been studied in discrete areas of the rat brain stem and hypothalamus. The changes in brain PNMT activity varied with the duration of the stress, were localized to a few brain areas, and the direction of the change varied with the area considered. PNMT was increased after acute immobilization in several areas of the brain stem: A2 area, the anterior part of the nucleus tractus solitarius, and the locus coeruleus. After 7 days of stress, significantly increased PNMT activity was found only in the A2 area and in the cerebellum. In the anterior hypothalamic nucleus, immobilization stress repeated for seven days resulted in a significant decrease in methyltransferase activity. These results implicate discrete, localized adrenaline-forming neurons in the central regulation of the stress response.