Met-enkephalin concentrations in the anterior pituitary gland were shown to decline dramatically within the first 24 h after reserpine treatment, with effects apparent as early as 6 h. This was followed by subsequent repletion and late augmentation of Met-enkephalin levels 3 weeks following reserpine. Treatment with the alpha-1-adrenergic agonist me-thoxamine had no effect, whereas the alpha-1-antagonist prazosin lowered Met-enkephalin concentrations. Treatment with the dopamine agonists bromocriptine or apomorphine had no effect, but haloperidol treatment increased anterior pituitary Met-enkephalin which was reversed by concomitant bromocriptine administration. We postulate that the changes in anterior pituitary Met-enkephalin following reserpine were related to alterations in the monoamine neurotran-smitters. Adrenergic and dopaminergic mechanisms may have opposing roles in the maintenance of Met-enkephalin concentrations in the anterior pituitary gland.