A 55-year-old right-handed man (patient DRB) had a major amnesic syndrome following extensive bilateral damage to the temporal lobe and basal forebrain, caused by herpes simplex encephalitis. His amnesia was both anterograde and retrograde. The retrograde amnesia spanned the five decades of his life, sparing only generic (semantic) material and shreds of previous experiences devoid of appropriate temporal and spatial placement. The anterograde amnesia encompassed both generic (semantic) and contextual (episodic) material. With the exception of preserved learning of a visuomotor skill, the patient did not show acquisition of any new information since his illness in 1975. Elementary perceptual, intellectual, and linguistic abilities remained intact. Because several anatomic and behavioral characteristics of this case are different from those of previously reported cases of amnesia, they may provide new insight into the neuroanatomic substrate of human memory.