The concentration of circulating hyaluronan was determined in rats after either the liver or the kidneys had been excluded from the systemic circulation. Both conditions caused an increase of the serum levels of hyaluronan. However, the rate of increase was more rapid in the animals with ligated hepatic vessels compared to those with ligated renal vessels. This in vivo investigation indicates that in the rat both kidney and liver systems are important for the removal of hyaluronan from the blood.