When rat adrenal glands are denervated, large increases in the amounts of enkephalin and enkephalin-containing polypeptides appear. In the normal gland, only trace amounts occur. One of the larger polypeptides (approximately 22,000 daltons) increases rapidly and by 48 hr following denervation, attains 20 times its original level. At this time, the levels of free enkephalins are essentially unchanged. By 96 hr, the 22,000-dalton polypeptide begins to decrease as free enkephalins and intermediate-sized enkephalin-containing polypeptides increase. This series of events is consistent with a precursor (22,000-dalton polypeptide)/product (enkephalin) relationship.