Abstract The effect of a range of saponins, commonly present in foods or dietary supplements, on the potential difference (PD) across the mucosa of the rat small intestine in vitro has been examined. Saponins from Gypsophila, guar, alfalfa, Quillaja, clover and liquorice together with glycoalkaloids from the potato and tomato were examined. The typical response was an immediate reduction in PD, although there was considerable variation in the response to particular compounds. Amongst the factors affecting the nature and magnitude of the de-polarizing effect were pH, solubility and the chemical form of the saponin. In agreement with the findings of others, glycyrrhizic acid, isolated from liquorice root, was found to exhibit a protective effect against the activity of a more potent saponin. The observations are discussed in the light of the known physiological activities of plant saponins and the regular, or excessive, consumption of certain foods or dietary supplements.