Differential ultrastructural features in the replicative cycle between a strain of human cytomegalovirus (CMV) and two strains (types 1 and 2) of herpes simplex virus (HSV) have been studied by electron microscopy. Either on the same or different host cell system four differential aspects have been constantly observed: a) presence in CMV infected cells of a large nuclear inclusion, lacking in HSV infected cells; b) envelopment of CMV capsids by microvescicular systems near the nuclear membrane, whereas HSV (types 1 and 2) takes envelope from the inner lamina of the nuclear membrane; c) presence in the cytoplasm of CMV infected cells of homogeneous dense material and dense microbodies, lacking in HSV infected cells; d) in extracellular space homogenous dense microbodies are present only in CMV infected cell cultures. Diagnostic usefulness of the above reported ultrastructural differences and their meaning on the basis of most recent data of the literature are discussed, with special concern to envelopment of two viruses and to the nature of homogeneous dense material observed in CMV infected cells.