We investigated the induction of apoptosis in cultured human fetal membrane cells infected with influenza virus type A. We found that influenza virus yield in supernatants of primary cultured chorion and amnion cells prepared from human fetal membranes increased 6 h after infection. Chromosomal DNA was fragmented into oligonucleosomes at 48 h after influenza virus infection in chorion cells but not in mock-infected chorion cells, mock-infected amnion cells or influenza virus-infected amnion cells. The DNA fragmentation in influenza virus-infected chorion cells was evident at 24 h after infection and depended on the multiplicity of infection at 48 h. Incubating influenza virus-infected chorion cells with ribavirin, an inhibitor of viral RNA synthesis, reduced the increase in virus yield and simultaneously blocked DNA fragmentation. These results suggest that both chorion and amnion cells become infected with influenza virus, but that influenza virus infection induces apoptosis in chorion, but not typical apoptosis characterized by DNA ladder formation in amnion cells. We further observed that influenza virus replication is associated with the induction of apoptosis.