Female rats given large doses of estrone developed increased permeability of the biliary tree as determined by an increase in the biliary clearances of sucrose and mannitol. Spontaneous bile flow and the choleretic response to dehydrocholate declined. Estrone reduced the clearance of sulfobromophthalein (BSP) at low plasma concentrations as well as the absolute rate of BSP excretion when plasma levels were above those required to saturate active transport. The findings are consistent with a postulate that estrogen cholestasis may involve enhanced diffusion of materials from bile to blood in addition to inhibition of active transport in the opposite direction.