A substance showing gastric secretion-inhibitory activity in rats was purified from defatted cell wall of brewer's yeast cells through extraction by autoclaving in distilled water, pepsin digestion, fractionation with ethanol, diethyl aminoethyl-Sephadex A-50 column chromatography and gel filtration on a Sepharose 6B column. The substance, named SP-I, markedly decreased gastric juice secretion in pylorus-ligated rats when administered intraperitoneally or intravenously at a dose of 2.5 mg/kg. SP-I reduced Shay ulceration by 81% (25 mg/kg×2, i.p.), aspirin ulceration by 56% (25 mg/kg, i.p.) and phenylbutazone ulceration by 82% (25mg/kg, i.p.). It was also shown that the decreases of hexosamine and sialic acid contents in gastric mucosa caused by aspirin administration in pylorus-ligated rats were significantly recovered by the administration of SP-I. SP-I, a new peptide-mannan (95% mannan, 3% peptide), showed a homogeneous pattern in ultracentrifugal analysis, and its molecular weight was estimated to be several hundred thousand daltons.