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The effects of an injection of vinblastine (Vbl) into the median eminence on the structure, fine structure and antidiuretic hormone (ADH) content of the hypothalamo-neurohypophysial system in the rat is reported. The animals were studied on days 3, 8 and 25 after the injection of 1 or 5 mM-Vbl (3 µl). Significant changes were observed only in the 5 mM-Vbl-injected animals. Their median eminence extracts showed a progressive accumulation of ADH whereas ADH depletion occurred in the neural lobe extracts. On day 8 after injection, the animals exhibited strong polidipsia although considerable amounts of ADH still remained within the neural lobe. The ADH content of the plasma samples was consistently below the sensitivity of the method (5 µu.). The light microscopic analysis showed accumulation of Gomori-stainable products in the median eminence and a striking depletion of this material from the neural lobe. Electron microscopy revealed accumulation of neurosecretory vesicles and other inclusions proximal to the site of injection in the median eminence together with some evidence of nerve fibre degeneration. Few neurosecretory terminals were found in the neural lobe of the 8-day experimental rats. They had been engulfed by pituicytes for digestion. Recuperation of the normal ADH content of both median eminence and neural lobe was found to occur on day 25 after the Vbl injection. Simultaneously, the neural lobe refilled with Gomori-positive materials and neurosecretory terminals reappeared. The results suggest (1) reversible blockade of axoplasmic transport at the site of the Vbl injection; (2) reversible degeneration of neurosecretory terminals and (3) reversible blockade of ADH release in the surviving terminals of the neural lobe.