Enrichment of the environment is an effective means of enhancing neuronal development and plasticity but its effect on the cross-modal compensation resulting from sensory deprivation has never been investigated. The present study used c-Fos immunohistochemistry and dextran-biotin neuronal tracing to examine the reorganization of sensory modalities in the brain of anophthalmic mutant mice (ZRDCT/An) raised in either enriched or standard environments. Auditory stimulation was found to elicit strong neuronal activation in thalamic and cortical structures that are normally visual. An important finding was that the latter auditory-evoked cortical activity was considerably enhanced in blind mice raised in the enriched environment. The axonal tracing study demonstrated auditory inputs from the inferior colliculus to the visual thalamus. This animal model will be useful for understanding neuronal mechanisms underlying some cross-modal sensory phenomena observed in blind or deaf humans.