The role of individual structures within the diencephalon for memory functioning is unknown. We present anatomic localization of lesions and a longitudinal neuropsychological profile of a young man who had a bilateral diencephalic stroke in the interpeduncular profundus arterial territory. MRI localized the lesions to the mamillothalamic tracts and inferior thalamic peduncle. The amnesia was characterized by severe impairment in explicit recall of new facts and events, while word-completion priming and remote memory were intact. We suggest that the memory deficit results from a disconnection of the diencephalon from the medial temporal region.