Electron microscopic appearance of the liver sinusoid was examined in rats fed alcohol chronically in a complete liquid diet or in sucrose-containing drinking water. The animals were kept on liquid diet (+/- alcohol) for 14 weeks or on sucrose-containing drinking water (+/- alcohol) for 12.5 weeks and sacrificed thereafter. To rule out possible artifact induced by fixation procedure, livers were fixed by immersion (no perfusion), immersion preceded by perfusion, and by perfusion with glutaraldehyde and examined with both scanning and transmission electron microscopy. Regardless of the mode of its administration, and of the fixation procedure used, alcohol induced similar changes in liver sinusoid ultrastructure. Such changes included disruption of the sieve-plate pattern of the sinusoidal endothelial cell fenestrations with the appearance of large gaps and resulting in a meshwork lining, wherein large areas of the sinusoid communicated freely with the underlying hepatocytes. Transmission electron microscopy complemented these findings. The results reported in this study demonstrate that alcohol-induced structural changes of the liver sinusoid in the rat are similar whether alcohol is fed via a liquid diet or in drinking water. Therefore, alcohol administration in drinking water may provide a simple, inexpensive, and convenient method of inducing structural changes in the rat liver sinusoid.