Primary cultivated amnion epitherial cells prepared from amnion tissue of human fetal membrane (Amnion-cells) were stimulated with influenza virus-hemagglutinin (IV-HA), fractionated from a commercialized IV-HA vaccine by DEAE Sephacel column chromatography. From 72—96 h after stimulation, chromosomal DNA fragmentation and the appearance of in situ TUNEL stained-positive cells were revealed. Amnion-cell DNA fragmentation was inhibited in the presence of glycophorin A or C purified from the human erythrocyte membrane fraction, but not inhibited with free N-acetyl-neuraminic acid. RT-PCR and Western blotting analysis showed that anti-oxidative enzymes were altered with incubation period, accompanied by the expression of the cellular oxidative stress-related caspase cascade. Pre-stimulation of Amnion-cells with hemin, a heme oxygenase-1 inducer, significantly attenuated IV-HA induced DNA fragmentation. It is concluded that IV-HA induces apoptosis in Amnion-cells, and that this apoptotic induction may be facilitated by certain sialoglycoproteins on the cell surface, and is related to changes in the intracellular redox condition.