The use of gene-knockout mice permits an increased insight into the role of specific transport proteins and membrane receptors in epithelial water and electrolyte transport. Data on the secondary coupling of water transport to Na-glucose cotransport and the mechanism of action of a number of prosecretory and proabsorptive enteric neurotransmitters are reviewed. Nitric oxide and some experimental treatments with therapeutic potential for cholera toxin-induced water and electrolyte secretion are discussed. A putative role of uroguanylin in intestinal bicarbonate secretion is explored.