The effect of media conditioned by concanavalin A-activated spleen cells (C-sup) on insulin release and its islet cell cytotoxicity were studied. In a functional study, C-sup significantly inhibited both basal insulin release and glucose-stimulated insulin release. Morphologically, C-sup had a destructive effect on isolated islets after 72 h incubation. Islet cell cytotoxicity was shown by lactate dehydrogenase (LDH) release assay after 5 days incubation with C-sup in a dose-dependent manner. These results suggest that acceleration of the onset of diabetes in young diabetes prone (DP) Bio-Breeding/Worcester (BB/W) rats following the injection of C-sup may depend on the suppressive and cytotoxic effects of C-sup on pancreatic islet cells.