The effect of insulin on the growth of fetal rat tissues was investigated using a transplant system. Paws from 15-day-old fetal rats were transplanted under the kidney capsule of 1-month-old syngeneic hosts, where they grew and differentiated normally. After 11 days of incubation, growth of transplants in hosts made diabetic by streptozotocin injection was reduced by 37% compared to growth in nondiabetic controls, but tissue differentiation and bone formation were normal in the absence of insulin. Injections of insulin (2 U, twice daily) into diabetic hosts restored paw growth to normal. Growth of transplants in hypophysectomized (HX) and in HX-diabetic hosts was reduced to the same degree (i.e. by 65%). Thus, the growth decrements produced by host hypophysectomy and diabetes are not additive. In contrast to the results with insulin-deficient hosts, the transplants failed to differentiate normally in the HX hosts. Injections of exogenous insulin (3 U, twice daily) to produce transient hyperinsulinemia failed to increase transplant growth in intact hosts over 11 days of incubation. The transplants were exposed to frequent periods of hyperglycemia and hyperinsulinemia by injecting 0.66 g glucose/100 g BW four times per day into intact hosts during 6 days of incubation. This treatment also failed to stimulate transplant growth. These results indicate that normal growth of transplanted fetal paw tissue is partially dependent on insulin, but whether the insulin acts directly or indirectly to support growth is not known. Supranormal insulin levels or frequent periods of hyperglycemia with hyperinsulinemia are not capable of producing overgrowth of the fetal paws. The HX, diabetic, and HX-diabetic host rats did not grow, as judged by tail length increase, and they lost weight. Accordingly, the juvenile host tissues have an obligatory dependence on insulin and GH for normal growth, but the fetal tissue is only partially dependent, because the paw transplants continued to grow in an internal milieu that was severely deficient in insulin and/or pituitary hormones. Overall, the results indicate that insulin is necessary for normal growth of the skeletal and connective tissues of the transplanted paw, but its effects are more growth supporting than growth promoting in these tissues.