Summary. Proliferation of islet cells may compensate for bothan increased peripheral insulin resistance and islet cell destruction but the capacity for regeneration may be genetically determined. For the latter reason, glucose-stimulated islet cell replication was estimated in both inbred C57BL/6J (BL/6) and C57BL/KsJ (BL/Ks) mice. Islets isolated from both strains were exposed to high concentrations of glucose in vitro or in vivo for a prolonged time period. This was achieved either by culturing the islets free-floating in a high glucose concentration medium for 3 days or implanting the islets intrasplenically in insufficient numbers to cure alloxan-diabetic syngeneic recipients. In both strains high glucose concentration culture was found to increase the autoradiographic labelling index of the islets but the replicatory activity decreased with age. The proliferative rate of the islet cells of the BL/6 mice was about twice as high as that of the BL/Ks mice irrespective of age and glucose concentration. Likewise, the labelling index of intrasplenic BL/6 islets implanted into alloxan-diabetic mice was twice as high as that of the islets implanted into alloxan-diabetic BL/Ks mice. The replicatory activity of the latter islets did not differ statistically from that of islets implanted into non-diabetic control BL/Ks mice. No differences in the rates of proinsulin and total protein biosynthetic rates were observed between high glucose concentration-cultured islets of the two mouse strains. The present resuits indicate that the proliferative response of pancreatic islets to a prolonged glucose stimulation may be genetically determined. This may play a significant role in the development of different diabetic syndromes both in laboratory animals and man.Key words: Inbred mouse strains, alloxan diabetes, islet culture, islet implantation, islet cell replication, autoradiographic labelling index, proinsulin biosynthesis.We have reported that intrasplenic transplantation of syngeneic pancreatic islets isolated from lean mice failed to cure obese hyperglycaemic mice, despite a considerable growth of the grafted islets [1]. In an attempt to elucidate the influence of hyperglycaemia on the growth of these islet grafts, syngeneic islets in numbers insufficient to cure diabetes (approximately 150) were implanted into alloxan-diabetic mice of two different inbred strains, C57BL/6J (BL/6) and C57BL/KsJ (BL/ Ks) [2]. The volume of the islets implanted intrasplenically into alloxan-diabetic BL/Ks mice decreased markedly, whereas that of islets implanted into BL/6 mice was usually unaffected. Some mice of the latter strain, however, became normoglycaemic and indeed, in these particular mice an increase of the volume of the implanted islets was found.The present study was carried out in order to elucidate to what extent a difference in islet cell replicatory activity of these two mouse strains contributes to the fate of intrasplenically implanted islets. For this purpose islets either were exposed to a high glucose environment in v...