This study used an item-based approach to explore the full range of lexical-semantic (word frequency and imageability) and sublexical characteristics (regularity and consistency) of stimulus items. Oral reading and spelling-to-dictation data from 72 adults with acquired alexia/agraphia due to stroke or progressive aphasia were analyzed to determine unique influences of lexical-semantic and sublexical variables on performance. Multiple regression analyses were performed for each etiology and lesion group (i.e., perisylvian stoke, extrasylvian stroke, perisylvian atrophy, and extrasylvian atrophy). As expected, word frequency had a significant influence on reading and spelling performance in almost all contexts. Of particular interest was the consistent finding that written language performance associated with left perisylvian damage was moderated primarily by lexical-semantic features of stimuli (frequency and imageability), whereas performance by those with left extrasylvian damage was strongly influenced by sublexical features of sound-spelling regularity and, to a lesser extent, consistency.