Double impregnation staining of tissue was used to study on thick sections the three-dimensional configuration of the peripheral endoplasmic reticulum in neurosecretory neurons of the supraoptic nucleus in control and water-deprived rats. According to the spatial organization of the endoplasmic reticulum, two types of neurons are described in this report: Type I neurons which predominated in control rats (70%) exhibited characteristically large lamellar structures connected to loosely anastomosed tubules. In type II neurons, which prevailed in water-deprived rats (85%) the endoplasmic reticulum had the appearance of a highly-developed network of interconnected tubules, with no lamellar structures. Double impregnation staining combined with high resolution radioautography after [3H]leucine administration showed that the tubular configuration of the endoplasmic reticulum was the main active site of protein synthesis by contrast with the lamellar components, whose activity seemed poor. In terms of protein synthesis, the three-dimensional configuration of the peripheral endoplasmic reticulum of the supraoptic neurons appeared therefore to be closely connected with their functional state. © 1979.