The replication process and cytopathic effects on the human amniotic fibroblast cells infected with human cytomegalovirus (HCMV) AD-169 were investigated by electron microscopy at various time interval, 0 to169 hours. At 2 h post infection(pi), some virus particles were present outside of the cells. The plasma membrane and the cell morphology at the fusion state were unchanged when compared to the controls. HCMV entered into the cells by fusion of the viral envelope with a limiting cell membrane. At 5 to 12 h pi, many viruses were round. The round cells contained condensed-nucleoli and cytoplasmic vacuoles. The nuclear membrane adjacent to the cytoplasmic inclusion (CI) exhibited prominent invagination. At 24 h pi, the virus particles were still shown in the cytoplasm, but not in the nucleus. Alterations as described above were seen in most cells. Most rounded cells had the early Nis and cytoplasmic granules. At 48 to 72 h pi, all of the cells were rounded and some of them were lysed. Nucleocapsids were observed around the periphery of the chromatin in some nuclei at 48 h pi, early Nis having predominantly the fibrillar network were demonstrated. The larger and presumably more mature Nis were observed, composed of a branching fibrillar network that demarcated one or more electron-lucent areas. The nucleo- capsids of all morphological types were budded through the inner nuclear membrane, either directly into the perinuclear cisterna or into sac-like mernbranous invaginations found commonly in the nucleoplasm. The rupturing of the nuclear membrane was not observed at these early stages. At late stages, 96 to 168 h pi, both the nucleus and the Nis were very large. Large, dense, spherical and homogenous bodies were often seen at the periphery of the nuclei. Condensed granules were investigated in the cytoplasrn instead of mitochondria, Golgi apparatus and ribosomes. The Nis occupied most of the nucleus and the fibrillar network of each cell were populated by a massive number of virus particles. Many virus particles were buded out through the plasma membrane, either directly of by reverse phagocytosis. Cell lysis was commonly occurred at 168 h pi.