Dietary water-soluble fiber supplementation elicits hypolipidemic effects. Propionate, the 3-carbon short-chain fatty acid derived from colonic fiber fermentation, has previously exhibited inhibition of cholesterol synthesis in vitro and may contribute to serum lipid lowering. This study examines the effect of colonic propionate absorption on serum lipids, sterol excretion and nutrient digestibility. Nine barrows were surgically cannulated at the distal ileum and cecum. Pigs received for 16 d continuous cecal infusions of either propionate (36 mmol/kg 0.75 daily) or saline (control) in a crossover design. Propionate infusion did not lower serum lipids, but increased total serum cholesterol by 15% (P less than 0.05) and LDL cholesterol by 15% (P less than 0.05). Differences in sterol excretion, ileal and fecal nutrient digestibilities, and weight gain were not detected between infusion treatments. The results suggest that propionate absorption does not result in decreased serum lipids and is not responsible for the serum lipid-lowering effects of water-soluble fibers.