The location and extent of brain changes that support recovery in chronic stroke is probably related to the structural integrity of the remaining cortex. However, little is known about the specifics of this relationship and how it influences treatment outcome in chronic stroke. To examine this issue, the current study examined frank brain damage and changes in cortical activation as predictors of language-treatment outcome in patients with chronic aphasia caused by stroke. Twenty-six patients received multiple MRI sessions before and after 30 h of aphasia treatment targeting anomia, an impairment in the ability to name common objects. Improved naming was associated with increased brain activation in the anterior and posterior regions of the left hemisphere, whereas damage to the posterior portion of the left middle temporal lobe and the temporal-occipital junction had a particularly negative effect on treatment outcome. Specifically, patients whose brain damage included regions commonly associated with lexical retrieval and phonological processing (e.g., Brodmann's areas 37 and 39) were less likely to show treatment-related improvement in correct naming compared with cases where the same areas were intact. These findings suggest that brain changes associated with improved naming ability in chronic aphasia rely on preservation and recruitment of eloquent cortex in the left hemisphere. In general, it seems likely that a similar relationship between cortical preservation and recruitment may also pertain to recovery from other functional impairments in chronic stroke.