Abstract-Influence of morphine on the fine structure of mitochondria in the cells of zona fasciculata in rat adrena 1 cortex was studied electronmicroscopically. By the administration of morphine to rats in a dose of 20 mg/kg, the specific honeycomb like structure of mitochondria in adrenocortical cells was observed to be transformed from vesicular forms into tubulo-vescicular or tubular ones, while the changed structure gradually diminished during repeated administration of the drug. Withdrawal of morphine caused an extensive re-transformation, while with a reinjection of the drug, a prompt restoration to the pretreated structure was observed. The feasibility of utilizing this transformation as an index of physical dependence liability has been discussed.Many pharmac ologists have focused their attenti on on the participation of hypophyseoadrenocortical a xis in the development of physical dependence on morphine or of tolerance to same, since chr onic administration of morphine causes a hypertrophy of the zona fasciculata of the adrenal cortex in rats, but not in those which have been hypophysectomized (1). As for loci of drug action in this axis, some questions still remain unanswered largely due to the limited resolving power of the light microscope for studying morphologically subcellular organelles of cortical or pituitary cells.On the other hand, some investigators (2-6) have demonstrated electron-microscopically that ACTH was capable of producing a certain ultrastructural transformation of mitochondria in the cell of zona fasciculata in the adrenal cortex. Furthermore, Kurosumi (7) in 1966 found a new type of granulated cell in the pituitary and also reported that ACTH is stored in the vesicles of that cell. These findings threw further light on biochemical evidence that ACTH activates enzymes located mainly in the adrenocortical mitochondria and plays an important role in corticosterone biosynthesis.On the assumption that these hypotheses are correct, additional structural alteration of the mitochondria in cortical cells should be evident following morphine administration.In addition, if a close relationship exists between development of physical dependence on morphine and processes of corticosterone biosynthesis involving ACTH action, it can