Cell-mediated autoimmunity is believed to influence the development of diabetes in BB rats. It has been suggested that the autoimmune destruction is due to lack of tolerance induction in early neonatal life caused by delayed maturation of the pancreatic beta cells. The present experiment has been initiated to investigate if there is any difference in in vitro cytotoxicity, and therefore antigenicity, to islet cells from neonatal, young and adult diabetes prone BB rats, and to establish the possible developmental difference in these rats compared to non diabetes prone Wistar Furth rats. Islets from rats of different ages were isolated, dispersed and 51C-labeled. In vitro cytotoxicity mediated by mononuclear spleen cells from newly diabetic BB rats was measured by counting gamma-ray emission from the culture supernatant after 16 h coincubation. We found that full adult-like islet cell maturation in BB rats--as evidenced by sensitivity to cytotoxicity--is not seen before the age of 8 to 21 days after birth. In contrast adult-like cytotoxicity to neonatal islets cells from Wistar Furth rats is seen already at the age of 8 days. Thus delayed islet cell maturation is a fact observed in BB rats.