We are using negative stain or a combination of osmium tetroxide fixation and negative stain to monitor the size homogeneity of lipid vesicle/liposome populations prepared by such techniques as sonication, extrusion, and gel filtration chromatography. Small sonicated vesicles up to about 50 nm in diameter seem sufficiently well preserved in negative stain for adequate size determination, although some flattening upon adherence probably does occur. Larger vesicles such as 100 nm extruded liposomes which contain a large aqueous core are likely to be flattened significantly in negative stain and may be partially stabilized with an osmium tetroxide fixation. The effectiveness of this fixation will in large part depend upon the degree of saturation of the lecithin species.