Influenza A virus (IAV) causes both activation and deactivation of the human neutrophil, which may, respectively, contribute to host defense against the virus and enhanced susceptibility to bacterial superinfection. We have shown that certain features of neutrophil activation by IAV are distinctive compared with activation by chemoattractants in terms of both the stoichiometry of the respiratory burst response and the signal transduction events that precede it. We here demonstrate that related myxoviruses as well as sialic acid-binding lectins elicit a respiratory burst response similar to that induced by IAV, in which hydrogen peroxide is formed with minimal accompanying superoxide generation. Brief preincubation of neutrophils with these agents fully inhibits subsequent activation by IAV, implying that they are binding to the same surface membrane components as IAV. Preincubation with Limax flavus agglutinin (LFA) does, in fact, substantially reduce binding of radiolabeled IAV to the neutrophil. This lectin, like IAV, both activates and deactivates the neutrophil. As in the case of IAV, LFA-induced activation (1) is mediated via stimulation of phospholipase C, (2) is pertussis toxin insensitive, and (3) entails a lesser contribution of calcium influx than is the case for chemoattractants.