The effects of a single and of repeated immobilization stress on the expression of the final enzyme involved in epinephrine biosynthesis, phenylethanolamine N-methyltransferase (PNMT), are described. A single immobilization (whether lasting 5 or 120 min) caused a severalfold increase of the adrenal PNMT mRNA level as measured 2 h after the beginning of the procedure. This elevation was of a transient nature, peaked 3-6 h after the 2-h immobilization, and returned to control values by 12 h after the stress. When the animals were immobilized for 2 h/day for seven consecutive days, an increase in content of PNMT mRNA of a similar magnitude was observed, which persisted for at least 2 days after the seventh immobilization. The immobilization-induced increase was completely abolished in hypophysectomized animals, whereas adrenal denervation failed to prevent it. These data suggest that the immobilization-induced increase in adrenal PNMT mRNA level depends primarily on pituitary-adrenocortical regulation.