This study describes the effects of high blood acetaldehyde concentrations on the intestinal absorption of ethanol and 2-butanone using an in situ single-pass perfusion technique on the rat intestine and the colored microsphere method to measure intestinal blood flow. We found that high blood acetaldehyde concentrations inhibit intestinal ethanol absorption in an inverse proportion to peak acetaldehyde concentrations, decrease intestinal blood flow, and inhibit intestinal absorption of 2-butanone. The decrease of the intestinal blood flow, induced by high blood acetaldehyde concentrations, is a major mechanism inhibiting intestinal ethanol absorption, but other mechanisms are also thought to inhibit absorption. Therefore, inhibition by high acetaldehyde concentrations is not the only factor affecting ethanol absorption.