Stripped rabbit descending colon mucosae were studied in vitro in modified Ussing chambers to determine the effects of AlF4- and vanadate on Cl- transport. Serosal additions of AlF4- and vanadate increase short circuit current (Isc) and tissue conductance, while luminal addition of the agents is ineffective. Addition of aluminium potentiates the effect of NaF on Isc. AlF4- and vanadate increase serosal-to-mucosal flux of 36Cl without affecting mucosal-to-serosal flux. The effects of these agents on Isc are markedly inhibited by serosal addition of bumetanide and depend on the presence of Na+ in the serosal bathing solution. The effects of AlF4- and vanadate on Isc are dependent on the presence of Ca2+ in the bathing solution, and are completely inhibited by indomethacin, but the effect of forskolin is not affected by the removal of Ca2+ from the bathing solution and the addition of indomethacin. AlF4- and vanadate significantly increase the level of inositol phosphate metabolites. The results indicate that AlF4- and vanadate increase Cl- secretion in the rabbit colon via an increase in prostaglandin synthesis which is mediated by the increase of intracellular Ca2+ concentrations.