1. Isolation of a self-emptying sac of rat small intestine in vivo halved the cell production rate in the crypts of Lieberkühn as measured by colchicine blockade.
2. Starvation for 48 h of rats with isolated intestinal sacs caused a further halving of cell production rate in the sac.
3. Infusion of distilled water into isolated intestinal sacs for 72 h caused a similar degree of stimulation of cell production in sacs in fed and starved rats, suggesting that the fall in cell production rate on starving a rat bearing an isolated sac is not due to the non-availability of the substances required for cell synthesis.
4. The possible contribution of innervation of the gut, and of systemic hormonal influences, on intestinal epithelial replacement is discussed.