The removal of hyaluronic acid (HA) from the blood-stream was studied in four normal human subjects after injection of high molecular weight preparations labelled with 3H in the acetyl position. The plasma half-life of the injected material ranged between 2.5 and 5.5 min. The daily turnover of HA in the circulation was estimated to be at least 150 mg. Its elimination was predominantly extrarenal, the upper molecular weight limit for renal excretion being 25 000. Evidence for rapid degradation was provided by the identification of 3H2O in urine. Calculations from the specific activity of urinary 3H2O indicated that approximately 55% of the acetyl content of the injected HA was completely oxidized within 3 h, and 85% within the first day. It is concluded that hyaluronic acid in the amounts currently used for therapeutic purposes should not accumulate significantly in the circulation.