Exposure of isolated rat hepatocytes to iodipamide resulted in its time dependent accumulation in the cells. No accumulation was observed with rat AS-30D hepatoma cells and isolated jejunal and ileal cells from guinea pig. At concentrations below 75 microM, the iodipamide uptake into the liver cells showed saturation kinetics with a Km of 55 microM and Vmax of 555 pmol/mg cell protein X min. At higher concentrations, a nonsaturable component with a permeability coefficient (P) of 1.02 X 10(-5) cm/s is superimposed on the hepatoselective iodipamide uptake. Uptake in liver cells was partially inhibited by DIDS, an irreversible inhibitor of bile acid and phalloidin uptake in liver cells. Iodipamide uptake was found to be dependent upon Cl- and was slightly reduced in the absence of Na+. Both SCN- and NO3- decreased iodipamide accumulation in liver cells whereas SO4(2-) enhanced the accumulation. As with bile acid and phalloidin uptake, monensin, valinomycin and gramicidin A markedly reduced iodipamide uptake in rat hepatocytes. The results support the hypothesis that the organotropic excretion of iodipamide is partially performed by an energy dependent carrier which is the bile acid transporter of hepatocytes.