There is increasing evidence for a role of pulmonary surfactant in asthma and allergic inflammation. In murine asthma models, recent studies have demonstrated that surfactant components downregulate the allergic inflammation. Therefore, we tested the hypothesis that in individuals with mild asthma, a natural porcine surfactant preparation (Curosurf) given before segmental allergen challenge can reduce the allergic airway inflammation. Ten patients with asthma and five healthy control subjects were treated in two segments with either Curosurf or vehicle followed by local allergen challenge. Six additional patients with asthma received Curosurf before allergen challenge in one segment as above, but the second segment was instilled with Curosurf without allergen challenge. Unexpectedly, surfactant treatment augmented the eosinophilic inflammation 24 hours after allergen challenge. A direct chemotactic effect of Curosurf was excluded. However, levels of eotaxin and interleukin-5 were increased in bronchoalveolar lavage after Curosurf treatment, whereas IFN-gamma-levels and numbers of IFN-gamma(+) T cells were decreased. Curosurf had no influence on spreading and retention of allergen determined by allergen uptake in mice. These findings demonstrate that treatment with a natural porcine surfactant results in an augmentation of the eosinophilic inflammation after allergen challenge that is more likely due to immunomodulatory effects than to biophysical properties of the surfactant.