Insulin-dependent diabetes mellitus (IDDM) results from a T cell-dependent autoimmune destruction of insulin-producing pancreatic beta cells. In the present study, expression of adhesion molecule ICAM-1 (CD54) on pancreatic beta cells was studied in normal, obese hyperglycemic (ob/ob), and nonobese diabetic (NOD) mice. Freshly isolated pancreatic beta cells from ob/ob mice did not express ICAM-1, but treatment of the cells with IL-1-beta, TNF-alpha, or INF-gamma strongly induced its expression as measured by immunofluorescence flow cytometry. The cytokines acted in a dose- and time-dependent manner. Maximal induction by either cytokine occurred at 24 hr and thereafter expression decreased, except for INF-gamma. Immunoprecipitation from IL-1-beta-treated beta cells demonstrated a cell-surface glycoprotein with an apparent molecular weight of 95 kDa. ICAM-1 expression was undetectable on pancreatic beta cells of normal and ob/ob mice as measured by immunohistochemistry. In NOD mice at different ages (1 to 6 months) ICAM-1 was also undetectable on beta cells, in contrast to the strong expression on infiltrating mononuclear cells. The present study indicates that mouse pancreatic beta cells, under certain conditions, can express ICAM-1.