The mechanism for the lowering of plasma cholesterol by water-soluble nonstarch polysaccharides (NSP) could involve alteration of intestinal viscosity leading to attenuated fat and steroid digestion and absorption. Alternatively, there may be direct inhibition of hepatic cholesterol synthesis by short-chain fatty acids produced by large bowel bacterial fermentation. A synthetic NSP, hydroxypropylmethylcellulose (HPMC), has been shown to lower plasma low-density lipoprotein (LDL) cholesterol in humans. This polysaccharide is not fermented by the large bowel microflora and has been shown to lower the plasma and liver cholesterol in hamsters, with no change noted in hepatic sterol synthesis. In further studies with hamsters, a linear relationship has been identified between plasma cholesterol and the logarithm of hydroxymethylcellulose viscosity. Only a relatively small increment in viscosity was necessary to achieve a maximal effect, suggesting that intestinal digestion may be quite sensitive to increased NSP intake.