In the past few years a number of studies have evaluated the contributions of different cytolytic pathways in the autoimmune destruction of pancreatic cells, which results in insulin-dependent (type I) diabetes mellitus. Conflicting results continue to emerge regarding the role of Fas-mediated apoptosis in -cell destruction. This is likely to reflect differences inherent to the model systems under investigation, as well as the pleiotropic nature of the genes that are involved in cytotoxicity. Despite these complications, it may be possible to reconcile some of these apparently conflicting results by considering that T-cell-mediated cytotoxicity can occur simultaneously by several mechanisms and that variables such as the cytokine milieu and the strength of the signal to the T cell received through the T-cell receptor complex may alter the relative contribution of each cytolytic pathway to -cell destruction.