According to a simple anatomical and functional model of word reading, letters displayed in one hemifield are first analysed through a cascade of contralateral retinotopic areas, which compute increasingly abstract representations. Eventually, an invariant representation of letter identities is created in the visual word form area (VWFA), reproducibly located within the left occipito-temporal sulcus. The VWFA then projects to structures involved in phonological or lexico-semantic processing. This model yields detailed predictions on the reading impairments that may follow left occipitotemporal lesions. Those predictions were confronted to behavioural, anatomical and functional MRI data gathered in normals and in patients suffering from left posterior cerebral artery infarcts. In normal subjects, alphabetic stimuli activated both the VWFA and the right-hemispheric symmetrical region (R-VWFA) relative to fixation, but only the VWFA showed a preference for alphabetic strings over simple chequerboards. The comparison of normalized brain lesions with reading-induced activations showed that the critical lesion site for the classical syndrome of pure alexia can be tightly localized to the VWFA. Reading impairments resulting from deafferentation of an intact VWFA from right- or left-hemispheric input were dissected using the same methods, shedding light on the connectivity of the VWFA. Finally, the putative role of right-hemispheric processing in the letter-by-letter reading strategy was clarified. In a letter-by-letter reader, the R-VWFA assumed some of the functional properties normally specific to the VWFA. These data corroborate our initial model of normal word perception and underline that an alternative right-hemispheric pathway can underlie functional recovery from alexia.