Ultrastructural and morphometric studies were undertaken on the hypothalamic supraoptic nucleus of streptozotocin-induced diabetic rats over a period of 1 y. At 3 d, a few dendrites showing electron-dense cytoplasm and dilated rER were dispersed in the neuropil among seemingly normal neuronal somata. At 1-6 months, the somata contained numerous vacuoles of various sizes which probably originated from fragmented and dilated rER. Numerous unidentifiable vacuolated and electron-dense neuronal profiles were also seen in the neuropil. At 9-12 months, the number of degenerating electron-dense axon terminals and dendrites was markedly increased in diabetic rats. Glial cells containing electron-dense debris in their cytoplasm were involved in phagocytosis. At all time intervals studied, the mean cross-sectional cell area and mean cross-sectional nuclear area of supraoptic nuclei neurons of diabetic rats were significantly increased in comparison with age-matched controls injected with normal saline. The causative factors for these changes are not clear. However, it is suggested that the osmotic stress caused by chronic dehydration in the diabetic animals may be partly or wholly responsible for these ultrastructural changes.