Animal models of insulin-dependent diabetes mellitus (IDDM) provide a uniquely valuable tool for understanding the pathogenesis of this disease. To the extent that they represent the human disease, they permit innovative approaches to its study. Four animal models--the BB rat, the nonobese diabetic mouse, the streptozocin-induced diabetic mouse, and the encephalomyocarditis virus-infected mouse--are reviewed. The salient characteristics of each model and the various techniques and immunotherapeutic agents used in conjunction with them to study prevention and reversal of IDDM are described, particularly the modulatory techniques directed at the cellular cytotoxic system, the regulatory immune system, and the beta-cell.