This study proposes to study the mechanism by which small dosages of methadone or other opioid inhibit the growth of young animals. We plan to further study the kinetics of the incorporation of precursors of RNA and protein and determine when this defect occurs during chronic methadone treatment and also when it ends. Morphological changes in tissues will be demonstrated by electron microscopy. The tissues to be examined include the peripheral nerves hypothalamus, pituitary, and viscera. The sural nerve has been found to show reduced diameter which is dose related as well as showing a significant reduction in the numbers of unmyelinated fibers. Collagen fibers are also greatly increased in the endoneurium of the sural nerves of mice treated for 4 weeks with methadone in a daily dosage of only 2 mg/kg. We plan to investigate neurohormonal influences because all the tissues of the treated mouse show metabolic deficits. We conclude that our original hypothesis of neurotrophic blockade is untenable because the organ most affected, the liver, is only sparsely innervated.