We examined at autopsy 47 cases (22 males and 25 females) of insulin-dependent diabetes mellitus (IDDM) from 21 hospitals in Japan to clarify the pathological changes that occur in the pancreas vs. those in control patients. The mean age was 39.7±13.9 (mean±SD) years, and the duration of IDDM from clinical onset was 13.1±6.5 years. Causes of death included renal complications, infections, acute diabetic complications such as ketoacidosis or hyper- or hypoglycemic coma, and atherosclerotic disease. This study revealed noticeable decreases in the islet area and beta cell area, and a slight decreases in the alpha cell area and preservation of the number of islets. Insulitis was found in only 1 case, representing 25% of the cases with a duration of IDDM of one year or less. Lymphocytic infiltration of the exocrine gland was seen in 22 cases (46.8%). Predominant phenotypes of the lymphocytes were T lymphocytes and macrophages. Fibrosis, fatty change and atrophy were also found. Although this is not a strictly age- and sex-matched study, the high incidence of lymphocytic infiltration of the exocrine pancreas indicates that the exocrine tissue as well as beta cells is the target of immune reactions in Japanese patients with IDDM.