The status of very long-term retention, together with detailed brain imaging correlates, is presented in two patients with disproportionately dense retrograde amnesia. The first patient suffered a severe closed head injury and was left with dense autobiographical amnesia for events that she had experienced prior to her injury. She showed relatively mild, patchy memory impairment on standard anterograde memory tests. Postinjury autobiographical memory was relatively spared. However, postinjury long-term knowledge acquisition was significantly impaired. The second patient also suffered a severe head injury and was left with marked retrograde amnesia for events that she had experienced prior to her injury. She also showed relatively mild, patchy impairment on standard anterograde memory tests. Using specially designed tests, this patient showed normal immediate learning and delayed recall using a range of materials, but displayed significantly faster rate of forgetting over a period of 6 weeks than control subjects who were matched on initial delayed levels of retention. In both cases, there was major pathology in the region of the left temporal lobe, with lateral structures being more affected than medial structures. Our findings provide further evidence relating to the independence of certain anterograde and retrograde memory mechanisms, and support recent observations (De Renzi & Lucchelli, 1993) that link some instances of retrograde amnesia to impairment in very long-term retention. The possibility is raised that some forms of retrograde amnesia, such as the present cases, represent a type of “disconnection syndrome,” whereby visual-semantic and other associations are disconnected from verbal representations of such associations. Lesions to intrahemispheric fasciculi or similar association fibers, in combination with lesions to critical anterior or posterior cerebral structures, may play an important role in such a disconnection.