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Bile salts can be cytotoxic to mucosal surfaces, because of their detergent properties. This is not normally seen under physiological circumstances in the gall-bladder. To further study normal mucosal defence mechanisms, the present study was performed to examine the effects of liposomes and hydrophilic bile salts on hydrophobic bile salt-induced release of radiolabelled glycoproteins from explants of guinea-pig gall-bladder. Glycoprotein release was correlated with the degree of hydrophobicity of bile salts, as determined by the retention factor in reversed-phase high-performance liquid chromatography. Hydrophobic bile salt-induced release of glycoproteins was reduced by liposomes and hydrophilic bile salts. The inhibitory effect of liposomes was directly related to the degree of saturation of their fatty acyl chains, and that of hydrophilic bile salts was related to the degree of hydrophilicity. These findings suggest that vesicles and hydrophilic bile salts may play a cytoprotective role against membrane damage passively caused by hydrophobic bile salts in the biliary system, and that such damage may occur according to the quantitative and qualitative imbalance among these factors.