A murine model of infection, in which immunocompetent or immunosuppressed interleukin-6-deficient (IL-6(-/-)) mice were infected intranasally with Aspergillus fumigatus conidia and were monitored for parameters of fungal colonization and innate and adaptive immunity, was used to assess the role of IL-6 in invasive pulmonary aspergillosis (IPA). The results indicate that IL-6(-/-) mice were more susceptible than wild-type mice to IPA. Susceptibility was associated with increased inflammatory pathology, decreased antifungal effector functions of phagocytes, and impaired development of protective type 1 responses. Exposure to exogenous IL-6 restored antifungal effector activity.