An evidence is accumulating that the oxygen tension exerts significant effect on the virus replication in vitro. When the in vitro oxygen tension is maintained at an in vivo physiological level, as a rule higher yields of human viruses are seen that at conventional culturing with access of an unphysiologically high oxygen concentration in ambient air. Although not fully understood, possible explanation for this phenomenon may be provided by a lowered interferon (IFN) output and increased cell replication which is often optimal at physiological oxygen tension. Furthermore, an indirect evidence suggests that the expression of some virus receptors is affected by oxygen tension. Also, the antiviral cell-mediated immunity is likely to be found oxygen tension-dependent as both the NK and cytotoxic T cell activities towards uninfected target cells are oxygen tension-sensitive. At present, the in vitro work with viruses at physiological oxygen tensions is hampered by the fact that cells adapt in the course of several weeks to the new oxygen tension. Whether viruses may adapt to different oxygen tensions is not clear. Workbenches combining safety in manipulation with hazardous viruses and the convenience of controlled gas atmosphere during both manipulation and long-term incubation have been developed. It is suggested that the in vitro virology should ensure that the physiological oxygen tension is better mimicked in the in vivo processes. Much work is to be done to determine the molecular interactions between oxygen tension-sensitive elements of the cell and infecting viruses. Of no lesser importance are the questions regarding the role of oxygen in virus tissue tropism, the cost-benefit of virus production at different oxygen tension levels, and the potential significance of oxygen tension for delivering gene effects to the selected target tissues.