In a previous study [Memory Cognit., in press], we demonstrated that some semantic concepts are more likely than others to be associated with specific personal memories, and that this autobiographical significance gives these concepts special status in long-term memory. In this paper, we explore the possible neural correlates of autobiographically significant semantic knowledge and examine whether or not autobiographical significance is a factor in determining patterns of semantic memory loss caused by brain damage. Using famous names that were rated on various attributes, including autobiographical significance, by control participants in a norming study [Memory Cognit., in press], we found that semantic dementia (SD) patients were more likely to recognize, identify and remember autobiographically significant episodes involving famous names that were rated high in autobiographical significance as compared to equally familiar names that were rated low. By contrast, people with Alzheimer's disease (AD) and people with medial temporal lobe (MTL) amnesia did not exhibit this preference for names rated high in autobiographical significance. Furthermore, in tests of free recall, recognition, fame judgment and speeded reading, semantic dementia patients demonstrated a performance advantage for autobiographically significant famous names, whereas the other patient groups did not. These findings suggest a critical role for medial temporal regions in the mediation of autobiographical memory and the interaction between personal experience and semantic memory. Theoretical implications are discussed.