A glycosulfatase activity towards human gastric sulfomucin was identified in the extracellular material elaborated by H. pylori, a pathogen implicated in the etiology of gastric disease. The purified enzyme exhibited maximum activity at pH 5.7 in the presence of 0.3% Triton X-100 and 100mM CaCl2, and displayed on SDS-PAGE an apparent molecular weight of 30kDa. The H. pylori glycosulfatase effectively caused desulfation of N-acetylglucosamine-6-sulfate and galactose-6-sulfate of the carbohydrate chains of mucins, as well as that of glucose-6-sulfate of glyceroglucolipids, but was ineffective towards galactosyl -and lactosylceramide sulfates which contain galactose-3-sulfate. The glycosulfatase activity towards human gastric sulfomucin was inhibited by an antiulcer agent, nitecapone, which at its optimal concentration (100 micrograms/ml) caused a 61% decrease in mucin desulfation. The results show that H. pylori through its glycosulfatase activity causes desulfation of sulfated mucins and glyceroglucolipids of the protective mucus layer, and that nitecapone is able to interfere with this detrimental action.