Different neuropsychological populations implicate diverse cortical regions in semantic memory: semantic dementia (SD) is characterized by atrophy of the anterior temporal lobes whilst poor comprehension in stroke aphasia is associated with prefrontal or temporal-parietal infarcts. This study employed a case-series design to compare SD and comprehension-impaired stroke aphasic patients directly on the same battery of semantic tests. Although the two groups obtained broadly equivalent scores, they showed qualitatively different semantic deficits. The SD group showed strong correlations between different semantic tasks - regardless of input/output modality - and substantial consistency when a set of items was assessed several times. They were also highly sensitive to frequency/familiarity and made coordinate and superordinate semantic errors in picture naming. These findings support the notion that amodal semantic representations degrade in SD. The stroke aphasia group also showed multimodal deficits and consistency across different input modalities, but inconsistent performance on tasks requiring different types of semantic processing. They were insensitive to familiarity/frequency - instead, tests of semantic association were influenced by the ease with which relevant semantic relationships could be identified and distractors rejected. In addition, the aphasic patients made associative semantic errors in picture naming that SD patients did not make. The aphasic patients' picture naming performance improved considerably with phonemic cues suggesting that these patients retained knowledge that could not be accessed without contextual support. We propose that semantic cognition is supported by two interacting principal components: (i) a set of amodal representations (which progressively degrade in SD) and (ii) executive processes that help to direct and control semantic activation in a task-appropriate fashion (which are dysfunctional in comprehension-impaired stroke aphasic patients). © The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.