Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia, characterized by poor executive control of semantic processing across verbal and non-verbal modalities; and (ii) Wernicke's aphasia, associated with poor auditory-verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well understood. Both patient groups exhibit some type of semantic 'access' deficit, as opposed to the 'storage' deficits observed in semantic dementia. Nevertheless, existing descriptions suggest that these patients might have different varieties of 'access' impairment-related to difficulty resolving competition (in semantic aphasia) versus initial activation of concepts from sensory inputs (in Wernicke's aphasia). We used a case series design to compare patients with Wernicke's aphasia and those with semantic aphasia on Warrington's paradigmatic assessment of semantic 'access' deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic 'blocking' effects). Patients with Wernicke's aphasia and semantic aphasia were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability-one that mapped onto classical 'syndromes' and one that did not-predicted aspects of the semantic 'access' deficit. Both semantic aphasia and Wernicke's aphasia cases showed multimodal semantic impairment, although as expected, the Wernicke's aphasia group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially 'beneficial' effects of stimulus repetition: cases with Wernicke's aphasia showed initial improvement with repetition of words and pictures, while in semantic aphasia, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the 'harmful' effects of repetition: the ability to reselect both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, patients with semantic aphasia and Wernicke's aphasia have partially distinct impairment of semantic 'access' but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks.