An epizootic of severe Cryptosporidium sp.–associated enteritis occurred in a group of 15 wild-caught juvenile rough green snakes (Opheodrys aestivus) at the Baltimore Zoo quarantine facility. All of the animals died with no premonitory signs. Histopathologic examination of the small and proximal large intestine of eight of the green snakes showed moderate to severe Cryptosporidium sp. infection and enteritis characterized by dense heterophilic and lymphocytic inflammatory infiltrates throughout the lamina propria with epithelial necrosis. Cryptosporidium sp. was also found in feces of an adult common garter snake (Thamnophis sirtalis) that was wild caught on zoo grounds and held in quarantine during the epizootic. After euthanasia, histologic examination of the garter snake showed a severe small intestinal Cryptosporidium sp. infection with only mild enteritis consisting of sparse heterophilic and lymphocytic infiltrates. There was no gross or histologic evidence of Cryptosporidium sp. gastritis in the nine snakes evaluated, and this is the first report of Cryptosporidium sp.–associated enteritis in snakes without gastric lesions.