We investigated the effects of damage to the medial temporal lobe (MTL) and anterolateral temporal cortex on semantic knowledge. We studied eight male controls, two patients with lesions limited to the hippocampal formation, three postencephalitic patients with extensive MTL lesions and variable damage to the lateral temporal cortex, and patient H.M. (whose lesion is limited mostly to the MTL, but who also has minimal damage to the anterolateral cortex). On 13 tests of semantic memory, patients with lesions limited to the hippocampal formation performed similarly to controls. Postencephalitic patients were mildly to moderately impaired on most tests. Patient H.M.'s performance was impaired on only a few tests and was less severely impaired overall than the three postencephalitic patients. A ranking of test scores showed a direct relationship between impairment and the extent of damage to lateral temporal cortex. These findings, and related findings from other studies, point to the importance of anterolateral temporal cortex for semantic knowledge. Patient H.M. performed uniquely in certain respects. For example, when providing definitions of objects, he made many grammatical errors. In contrast, the other patients with large MTL lesions made no more errors than those made by controls. Considering that H.M.'s lesion, both medially and laterally, is less extensive than the lesions in these other patients, it appears unlikely that his shortcomings in language production are related to his temporal lobe lesion. Hippocampus 2002;12:520–533. Published 2002 Wiley-Liss, Inc.