After oral or intravenous administration of 14C-rhein to male rats, blood concentrations were measured for up to 48 h. Both mean blood level curves and also the calculated pharmacokinetic constants show a fairly good conformity. Organ distribution was measured up to 2 days after intravenous and up to 7 days after oral application. In most organs the activity is lower than in plasma with very low values in testicles and in brain. Higher values are found in the main excretion organ, the kidney. The plasma protein binding of 14C-rhein is very high both in rat and human serum. Absorption in or adsorption on erythrocytes is very small. Rhein and its metabolites are excreted by kidney and liver. Biliary-excreted rhein metabolites are easily reabsorbed and finally excreted with urine. In bile, there are mainly two conjugated metabolites of rhein, whereas in urine also larger amounts of rhein and one or two additional metabolites can be detected. All metabolites seem to be conjugates, because they can be split by glucuronidase/arylsulfatase to rhein. Rhein is absorbed after oral application by about 50-60% and after administration into the colon by about 50%.