Juvenile onset diabetes in humans exhibits an autoimmune sequel in its pathogenesis that is thought by many to be a contributing factor in the development of the diabetic condition. Extensive sequential analyses of the pathological events culminating in the inappropriate hyperglycemia have not been reported and thorough study of these conditions is unlikely considering the inability to obtain the appropriate tissues at the time intervals required. This project is designed to determine if comparable immunobiological parameters exists in the pathogenesis of spontaneous diabetes in a closed colony of diabetic Abyssinian guinea pigs and, if such exist, to examine in a sequential manner the pathogenic processes leading to the diabetic condition. The spontaneously diabetic guinea pig exhibits many of the characteristics of human juvenile-onset diabetes such as spontaneous occurrence, hyperlycemia, glycosuria, polyuria and polydipsia along with comparable histopathological lesions. The guinea pig will be tested for evidence of comparable forms of humoral immune system involvement in the pathogenesis of diabetes such as the occurrence and sequential distribution of islet cell antibodies as well as for anti-insulin antibodies, lymphocyto-toxic antibodies, immune complexes and antibodies to the endocrine tissues. Concurrent with the studies of autoimmunity will be an examination of the metabolic and histologic disturbances occurring within the same time frame to assess the degree of synergism that might be involved in the pathogenesis. These studies are believed to be essential for answering the questions concerning the suitability of the guinea pig as an animal model of human juvenile diabetes mellitus.