Jejunal fluid secretion induced by perfusion with oleic acid can be reduced by the addition of cholesterol. The present study was performed to test the specificity of this effect by comparing the effects of cholesterol with that of a plant sterol, beta-sitosterol during perfusion of the jejunum in healthy volunteers. In addition, we compared the solubilities of cholesterol and beta-sitosterol in micellar solutions and their jejunal absorption rates. One millimolar beta-sitosterol was as effective as 1 mM cholesterol in reducing jejunal fluid secretion induced by 6 mM oleate (n = 7). In mixed micellar solutions consisting of 10 mM taurocholate and 6 mM oleate, solubility of beta-sitosterol is about one third of cholesterol solubility. When cholesterol was gradually replaced by beta-sitosterol in the incubation mixture, beta-sitosterol reduced cholesterol solubility to a greater extent than would be expected from an equimolar replacement of cholesterol by beta-sitosterol. Absorption of beta-sitosterol was limited by its solubility in mixed micellar solutions and both sterols were absorbed at equal rates as long as their solubility limits were not exceeded (n = 5).