The degradation of sulfated glycosaminoglycans by rat gastric mucosa was investigated. The presence of beta-glucuronidase, N-acetyl-beta-hexosaminidase, sulfohydrolase and a hyaluronidase-like enzyme was demonstrated. The degradation of chondroitin 4-sulfate by gastric mucosal enzymes appeared to progress by a concerted mechanism, as shown by inhibition studies with saccharolactone and acetamidogalactonolactone and by addition of the limiting enzyme, beta-glucuronidase. Sulfated oligosaccharides containing less than 20 residues are poorly degraded, and it appears that the gastric enzyme complex prefers, for reasons unknown, high molecular weight substrate. A collaborative study with Drs. Oronsky and Buermann of Lederle Laboratories demonstrated the concerted mechanism of degradation of chondroitin 4-sulfate by human polymorphonuclear leukocytes. The latter finding may have implications for rheumatoid arthritis.