We investigated the effect of a fungal component, soluble beta-glucan, on secretory functions of murine alveolar macrophages (AMs) in vitro. Stimulation by beta-glucan (500 microg/mL) or interferon-gamma (IFN-gamma; 100 U/mL) alone had a slight effect on AM functions, but when AMs were incubated together with beta-glucan and IFN-gamma, the production and secretion of some immune mediators, such as nitric oxide, interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha), were markedly augmented. This combined effect of beta-glucan and IFN-gamma was based on a priming effect of IFN-gamma, because prestimulation with IFN-gamma followed by beta-glucan induced high nitric oxide production of AMs, but reversal of the sequence of treatments had only a slight effect. We also found that preincubation of AMs with IFN-gamma enhanced the binding of fluorescein-labeled beta-glucan on the AM surface, and this increased binding was abrogated to the control level by the addition of three species of soluble unlabeled (1-->3)-beta-D-glucans but not by soluble alpha-glucan. These data imply that the priming effect of IFN-gamma on the AM response to beta-glucan was dependent, at least in part, on the enhancement of beta-glucan specific binding sites on the AM surface. It was suggested that IFN-gamma is one of the principal factors controlling the pulmonary immune system against both severe fungal infection and inflammation via AM activation at the alveoli.