A comparison was made of the actions of substance P, prostaglandin F2 alpha (PGF2 alpha), histamine and carbachol on the membrane potential and conductance of the longitudinal smooth muscle of the taenia of the guinea-pig caecum using the double sucrose gap apparatus. The increases in conductance produced by the four drugs during matched depolarizations in the sucrose gap were not significantly different and they were substantially larger than the increase in conductance brought about during the same depolarization produced by passing outward current. In sucrose-substituted, Na- and Cl-deficient solution the increases in conductance and depolarization due to carbachol, substance P, and PGF2 alpha were attenuated to a similar extent. The depolarization due to histamine under these conditions was reduced to a significantly greater extent than that due to carbachol. In Tris-benzene-sulphonate substituted Na- and Cl-deficient solution the responses due to carbachol and histamine were attenuated to a similar extent. This suggests that sucrose addition may have a specific effect on the histamine response. In Tris-substituted Na-deficient solution the increases in conductance and depolarization produced by substance P, histamine and carbachol were attenuated to a similar extent. The depolarization due to PGF2 alpha was reduced by a significantly greater amount which may be due to unmasking an inhibitory effect that was sometimes apparent in normal solution. In benzenesulphonate-substituted, Cl-deficient solution the increases in conductance and depolarizations produced by moderate concentrations of PGF2 alpha, histamine and carbachol were attenuated to a similar extent. The response to substance P was little affected. In glucuronate-substituted, Cl-deficient solution the increases in conductance and depolarizations due to substance P and carbachol were attenuated to a similar extent. This result, and the observation that the depolarization to large concentrations of carbachol was not reduced in benzenesulphonate-substituted, Cl-deficient solution, suggest that benzenesulphonate interferes with the reactions of the non-peptide stimulants with their respective receptors. The similarities in the effects of activating the four types of receptor under some conditions could be explained if they all acted on the same population of receptor-operated channels. In addition it seems that PGF2 alpha acts also on a population of inhibitory receptors, sucrose interferes with histamine's action, and benzenesulphonate interferes with the reactions of non-peptide stimulants with their respective receptors.