Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.