The effects of modification of the levels of endogenous plasma insulin on intestinal epithelial cell proliferation were investigated in rats maintained by total parenteral nutrition (TPN) using either a TPN diet that was high in glucose, or a low glucose (hypocaloric) TPN diet and in orally fed rats (normal and sham operated). The rats were put on their respective treatments for 7 days and were then injected with vincristine sulphate to arrest cells as they entered metaphase. Intestinal tissue was fixed for the determination of crypt cell production rate (CCPR) and blood plasma was taken for hormone radioimmunoassay. Sham operation had no effect on either plasma hormone levels or on CCPR. The standard TPN diet was associated with significantly reduced levels of gastrin, peptide YY and enteroglucagon. Gastrin and PYY were further reduced by the hypocaloric diet. However, plasma insulin was much increased in the TPN but not in the hypocaloric group. Small intestinal CCPR was reduced in the TPN groups, but no difference was observed between the standard and the low calorie TPN diets. The lack of difference in CCPR between the two TPN diets despite the massive elevation of plasma insulin strongly suggests that insulin does not have a substantial role in the control of gastrointestinal epithelial cell renewal.