We studied the histo- and immunopathology of the endocrine and exocrine pancreas and a number of other organs in a new insulin-dependent diabetes mellitus (IDDM) rat model (LEW.1AR1/Ztm- iddm rat). The pancreas of the acutely diabetic animals showed an inflammatory infiltrate, involving all islets and ducts. The islet infiltrate was composed mainly of ED1-positive macrophages and T lymphocytes, comprising a large number of CD8(+) lymphocytes and a few CD4(+) lymphocytes. In addition, the islets displayed apoptotic cells, characterized by condensation and fragmentation of nuclear chromatin. These cells were identified as beta cells by insulin immunostaining. Other endocrine and exocrine glands, including adrenals and thyroid, as well as salivary and submandibular glands, were unaffected. Organs from the digestive tract or systemic circulatory system, including small intestine, liver, heart, and lung also showed no involvement. The kidney was intact in acutely diabetic rats. However, 6 months after diabetes manifestation, pathological changes compatible with a diabetic nephropathy had developed, affecting both the glomerula and the proximal tubular segments. It was concluded that the autoimmune process in this new IDDM rat model is restricted to the endocrine pancreas and leads to apoptotic beta cell destruction.