One would expect that a lifetime of experience recognizing letters would have an important influence on the visual system. Surprisingly, there is limited evidence of a specific neural response to letters over visual control stimuli. We measured brain activation during a sequential matching task using isolated characters (Roman letters, digits, and Chinese characters) and strings of characters. We localized the visual word form area (VWFA) by contrasting the response to pseudowords against that for letter strings, but this region did not show any other sign of visual specialization for letters. In addition, a left fusiform area posterior to the VWFA was selective for letter strings, whereas a more anterior left fusiform region showed selectivity for single letters. The results of different analyses using both large regions of interest and inspections of individual patterns of response reveal a dissociation between selectivity for letter strings and selectivity for single letters. The results suggest that reading experience fine-tunes visual representations at different levels of processing. An important conclusion is that the processing of nonpronounceable letter strings cannot be assumed to be equivalent to single-letter perception.