Studies in dogs, rats, hamsters and rabbits will be directed at understanding basic mechanisms of bile secretion, bile duct function and gallbladder function. The osmolality of bile will be measured during administration of bile salts and gastrointestinal peptide hormones, and the effects of vasopressin, pharmacologic transport inhibitors and increased ductal pressure will be studied. The source and pathways of bile water will be studied by measurement of the transit time distributions for various inert solutes. Evidence for or against intercellular water transport will be sought. The constancy of biliary cholesterol and lecithin excretion will be measured during protracted bile salt infusions in order to appraise the regulatory role of lipid synthesis vs passive physico-chemical lipid-bile acid coupling. The comparative response of lipid excretion to a variety of normal bile acids will be measured. The effects on lipid excretion of compounds known to cause cholestasis (e.g. hyodeoxycholic and lithocholic acids, indocyanine green, alpha napthyl isothiocyanate) will be studied. Gallbladder absorptive activity will be measured in vivo under the influence of neurohypophyseal and gastrointestinal peptide hormones, phosphodiesterase inhibitors, parasympathetic blockade (or vagotomy), cholinergic stimulation and cholera toxin. This information is relevant to an understanding of human cholelithiasis and of the cholestatic syndromes.