Asthmatic attacks are often precipitated by viral respiratory infections. The mechanism of virus-induced asthma is still unclear. Interferon could be an important mediator in virus-induced hypersensitivity reactions, because interferon is induced by some respiratory viruses, and it can enhance IgE-mediated histamine release in vitro. We studied the effect of common respiratory viruses, including both interferon inducers and non-interferon inducers, on IgE-mediated leukocyte histamine release. Leukocytes from healthy, nonallergic donors were exposed to different strains of respiratory viruses, and basophils were challenged with antibody to IgE to release histamine. We found that the viruses are capable of enhancing IgE-mediated histamine release in the presence or absence of interferon. Our results suggest that although interferon may play a role in virus-induced hypersensivity reactions, other mechanisms probably also play a significant role.