Chondroitin sulfate is administered as a drug to man by intravenous, intramuscular or oral route. However, few data are available on the metabolic fate of exogenous chondroitin sulfate in man. After intravenous administration of 0.5 g of chondroitin sulfate to healthy volunteers, the plasma level decreases according to a two-compartmental open model. The half-lives of distribution and elimination are 25.5 +/- 6.6 and 281 +/- 32 min, respectively. The volumes of central and tissue compartments are 6.0 +/- 1.0 and 22.9 +/- 7.7 l, respectively. More than 50% of the administered chondroitin sulfate is excreted with urine during the first 24 h as high and low molecular weight derivatives. After oral administration of 3 g of chondroitin sulfate to 12 healthy volunteers, a main peak (11.4 +/- 3.7 micrograms/ml) preceded by a lower peak is observed after 190 +/- 21 min. The elimination half-life is 363 +/- 109 min. The absolute bioavailability following oral administration calculated from AUC of plasma concentration is 13.2%. A peak of oligo- and polysaccharides with a molecular weight lower than 5000 Daltons derived from partial digestion of exogenous chondroitin sulfate is also present in plasma. These observations indicate that the metabolic fate of exogenous chondroitin sulfate is similar in man and in experimental animals.