We examined the in vivo cell-mediated immune response in infants with respiratory syncytial virus (RSV) infection in order to gain information about the pathogenesis of severe RSV disease in infancy. Semiquantitative reverse transcription-polymerase chain reaction and three-color flow cytometry were used to determine the levels of messenger RNA (mRNA) for interferon (IFN)-gamma in peripheral blood mononuclear cells, and the distribution of lymphocyte subsets in infants with acute RSV infection. The findings were correlated with the severity of the patients' illness and the production of RSV-specific IgE antibodies (RSV-IgE). Significantly lower IFN-gamma levels and T-lymphocyte counts in the acute phase of illness were observed in infants with severe RSV disease than in those with a milder clinical course of illness. The induction of RSV-IgE was not related to IFN-gamma levels in the acute phase of illness, but rather correlated with IFN-gamma expression during convalescence. The data indicate that reduced IFN-gamma expression may be an important factor in the pathogenesis of severe RSV disease in infancy.