Several erythromycin derivatives were tested for their effect on the function of the isolated, perfused rat liver. Erythromycin estolate inhibited bile output, sulfobromophthalein (BSP) removal from the perfusate and the biliary excretion of this dye. The propionate congener also induced a significant decrease in these parameters, at least as great as that caused by estolate. Other derivatives showed lesser effects on these parameters of liver function. Even at drug concentrations so low that rate of bile flow and removal of BSP were unaffected, all derivatives decreased BSP biliary excretion.