The aim of the present study was to correlate the islet expression of the apoptosis-associated factors Fas/Apo-1, FasL, ICE and perforin with the progression of beta-cell destruction in non-obese diabetic (NOD) mice. For this purpose, thymus and isolated pancreatic islets from male and female NOD mice of 5 and 15 weeks of age were subjected to immunoblot analysis. Islet expression of the Fas/Apo-1 receptor and ICE were increased in islets from female mice 15 weeks of age as compared to corresponding males. No Fas/Apo-1 or ICE signal was observed in the 5-week-old mice. The expression of perforin increased both in islets and in thymus with age and female gender. Islet expression of FasL could not be detected. Culture of isolated islets from NMRI mice in the presence of interleukin-1beta (IL-1beta) induced the expression of ICE. The present results support a direct role of the Fas/FasL and the perforin systems in the autoimmune destruction of insulin producing cells [corrected].