The obese-hyperglycemic syndrome is well characterized in adult mice. However, little is known about islet morphology and function at an early age when obese mice islets start to proliferate. We have now studied islet morphology and functional development in obese-hyperglycemic mice (Umeå ob/ob) and their lean littermates at ages < or = 38 days. The weight of obese mice began to increase more than that of the lean littermates at days 8 to 12. At day 18, clinical diagnosis of the ob/ob syndrome could be made with 100% certainty. Islets from obese mice started to show enhanced growth rate during week 4, coinciding with the time of onset of hyperglycemia. 3H-thymidine labeling index is enhanced in ob/ob mice from day 22. Insulin secretion in islets from mice aged 18 to 21 days was the same in obese and lean mice from the same litter. At days 30 to 33, second-phase release and islet insulin content were decreased in islets from obese animals, but were restored after an overnight fast. It is likely that the hyperglycemia rather than increased insulin demand triggers increased beta-cell growth.