In biochemical and immunocytochemical comparisons of adhering junctions of different epithelia, we have observed differences in molecular composition not only between the intermediate filament-attached desmosomes and the actin filaments-anchoring adherens junctions but also between desmosomes of different tissues and of different strata in the same stratified epithelium. In addition we now report cell type-specific differences of molecular composition and immunoreactivity in both desmosomes and adherens junctions of certain simple epithelia. Whereas the zonula adhaerens of human intestinal and colonic epithelial cells, and of carcinomas derived therefrom, contains the additional armadillo-type plaque protein ARVCF, this protein has not been detected in the zonula adhaerens of hepatocytes. Similarly, plakophilin 3 is present in the desmosomal plaques of intestinal and colonic cells but appears to be absent from the hepatocytic desmosomes. We suggest that these profound compositional differences in the junctions of related simple epithelia are correlated to functional differences of the specific type of epithelium.