Rhabdomyosarcoma (TE) and cervical carcinoma (MS) cells 24 h previously brought from medium with a PO2 of 18 kilo Pascal (kPa) (ambient air) to PO2 of 6 or 3 Kpa (in vivo physiologic values) were infected with Sendai virus, and the interferon (IFN) and virus production was followed in the ensuing 24 h period. With TE cells the IFN production decreased when moving from 18 to 6 Kpa and ceased completely at 3 Kpa, while the virus production responded inversely. MS cells produced most IFN at the lowest oxygen tension, and virus production was only moderately affected. Growth for three months at the three different oxygen tensions prior to infection reduced the difference in IFN production at the different oxygen tensions. On the same target cells different human virus responded in different ways to the tested oxygen tensions. It is concluded that mimicking the in vivo situations might require primary cultures of virus and cells to be started and passaged at in vivo physiological oxygen tensions.