A new hypolipidemic substance, lentysine, was isolated from a species of mushrooms, SHIITAKE, or Lentinus edodes Sing. The present paper deals with the effect of lentysine on serum and tissue lipids in rats and rabbits. Effect on serum and liver lipids in intact male rats: Lentysine was administered orally, once daily, for 14 days to six-week-old male rats of Sprague-Dawley strain. Determinations of serum lipids showed that a lower dosage of lentysine caused a significant decrease in the levels of total cholesterol, phospholipid and triglycerides. Lentysine was more potent than clofibrate. However, lentysine treatment showed no effect on liver lipid levels. Effect on serum and liver lipids in cholesterol-fed rats: A marked increase in serum lipid levels was produced by feeding rats a lipid-enriched diet containing 2% cholesterol, 1% cholic acid, etc. Lentysine markedly depressed serum total cholesterol, phospholipid and triglyceride levels at a dose of 1mg/kg/day, but had no lowering effect on liver lipid levels. Effect on serum and tissue levels and atheromatous lesion of the aorta in cholesterol-fed rabbits: Male albino rabbits, weighing about 2.5kg, were maintained for 8 weeks on a rabbit chow augmented with 0.6% cholesterol in 3% cottonseed oil. The animals received the cholesterol diet supplemented with lentysine, starting from 2 weeks after the onset of cholesterol feeding. Administration of lentysine resulted in great depression of serum cholesterol, total lipid, phospholipid and triglyceride levels, but no reduction of liver lipid concentrations. Atheromatous lesion of the aorta seemed less severe in the lentysine group, but the difference from control value was not statistically significant. It is evident that β-sitosterol treatment resulted in lowered serum-and liver-lipid levels and less severe atheromata. Effect on serum steroid pattern: Male S. D. rats received lentysine 250mg/kg daily for 14 days. Examination by gasliquid chromatography of the non-saponifiable fraction of rat serum revealed no apparent difference in steroid pattern between lentysine-treated animals and control. It seems that lentysine displays a potent hypocholesterolemic activity without any apparent accumulation of other steroids.