The effects of perfusing solutions of different composition into the distal ileum of the rat, on glucose or galactose absorption from the jejunum has been determined in vivo. The rate of glucose absorption via the active, phlorhizin-sensitive pathway was increased significantly when either glucose or maltose were present in the lower ileum. In contrast, the presence of galactose, lactose and fructose produced only minimal effects on active glucose absorption. The phlorhizin-insensitive component of glucose absorption was unaffected by the presence of sugar in the distal region. Perfusion of glucose into the ileum enhanced the active uptake of the poorly metabolized hexose, galactose, from the jejunum. The administration of cycloheximide abolished the increase in active glucose absorption induced by distal maltose perfusion. The response to distal glucose (a) required the sugar to be perfused for a minimum of 3 h before increases in absorption became significant, and (b) was not dependent on distal glucose absorption by the phlorhizin-sensitive pathway. The possible mechanisms involved in this adaptive response are discussed. The enhancement of jejunal absorption may be important in man in conditions where glucose is present at abnormally high levels in the distal ileum.