We tested the effect of inactivated influenza A virus on the response of human T lymphocytes to several stimuli. Our results demonstrate that the response to both phytohemagglutinin A (PHA) and anti-CD3 was substantially enhanced by pre-exposure of peripheral blood mononuclear cells (PBMC) to heat-inactivated viral particles, whereas no effect was noted on the proliferative response of PBMC to IL-2. In addition to cell proliferation, exposure of PBMC to viral particles increased the secretion of interferon (IFN)-γ during stimulation with anti-CD3 antibody and PHA. The costimulatory effect of influenza A virus was reduced by 40% in the presence of 0.1 mM sialic acid. The possible mechanisms involved in the costimulatory effects of influenza A virus are discussed.