A key issue in developmental neuroscience is the role of activity-dependent mechanisms in the epigenetic induction of functional organization in visual cortex. Ocular blindness and ensuing visual deprivation is one of the rare models available for the investigation of experience-dependent cortical reorganization in man. In a PET study we demonstrate that congenitally blind subjects show task-specific activation of extrastriate visual areas and parietal association areas during Braille reading, compared with auditory word processing. In contrast, blind subjects who lost their sight after puberty show additional activation in the primary visual cortex with the same tasks. Studies in blind-raised monkeys show that crossmodal responses in extrastriate areas can be elicited by somatosensory stimulation. This is consistent with the crossmodal extrastriate activations elicited by tactile processing in our congenitally blind subjects. Since primary visual cortex does not show crossmodal responses in primate studies, the differential activation in late and congenitally blind subjects highlights the possibility of reciprocal activation by visual imagery in subjects with early visual experience.