The cadherin family consists of several homophilic adhesion molecules that, together with their intracellular binding partners the catenins, are known to mediate axonal navigation, target recognition, and synapse formation during development. Here, we have examined the potential role of these molecules in axonal sprouting induced in the adult brain. Over a period of 3 to 60 days, an episode of pilocarpine-induced status epilepticus (SE) led to sprouting of hippocampal mossy fibers both into the CA3 pyramidal cell layer and the inner molecular layer of the dentate gyrus (DG). We found focal up-regulation of N-cadherin, beta-catenin, and alpha-catenin immunoreactivity within segments of the CA3 pyramidal cell layer with pronounced neuron loss that was associated with the development of mossy fiber sprouting. In contrast, expression of these 3 molecules was unaltered in the DG molecular layer despite mossy fiber sprouting in this area. The levels of E-cadherin immunoreactivity were altered prior to the detection of mossy fiber sprouting, with a general reduction in the neuropil and increased expression in CA1/CA3 pyramidal cell somata. Our results imply that members of the cadherin/catenin families undergo specific spatiotemporal patterns of regulation, which may be important in axon target recognition and synapse formation during lesion-induced sprouting.