Glucose loading of rats made thiamin deficient by dietary deprivation of thiamin and the administration of pyrithiamin (40姯100 g; i.p.) can precipitate precipitates an acute neuropathy, a model of Wernicke's encephalopathy in man. neurological disturbances (Zimitat and Nixon, Metabolic Brain Disease 1999; 14: 1-20). Immunohistochemical detection of Fos proteins was used as a marker to identify neuronal populations in the thiamin-deficient rat brain affected by glucose loading. As thiamin deficiency progressed, the extent and intensity of Fos-like immunoreactivity (FLI) in brain structures typically affected by thiamin deficiency (the thalamus, mammillary bodies, inferior colliculus, vestibular nucleus and inferior olives) were markedly increased when compared to thiamin-replete saline-treated controls. Glucose loading for 1 to 3 days further significantly increased the intensity of FLI in these same regions, providing a link between consistent with a dependence of Fos expression on the glucose load carbohydrate metabolism and the loci of pathology in the brains of thiamin deficient animals as well as on thiamin deficiency. The timed acute changes that follow a bolus glucose load administered to thiamin-deficient animals may provide a sequential account of events in the pathogenesis of brain damage in this model of Wernicke's encephalopathy.