RATIONALE: Rhinoviruses, which are members of the picornavirus family, are important causes of asthma exacerbations and early life wheezing illnesses that are associated with increased asthma risk. Given the absence of natural rhinovirus infections in rodents, we used attenuated mengovirus, a picornavirus whose wild-type form causes systemic infections in its natural murine hosts, to induce respiratory infections in mice, which we hypothesized would serve as a useful model for neutrophilic inflammatory processes in human rhinovirus infections. METHODS: BALB/c mice received intranasal inoculations with active or UV-inactivated attenuated mengovirus or vehicle. On various days postinoculation, inflammatory cells and mediators were assessed in the bronchoalveolar lavage (BAL) fluid and lung tissue, and pulmonary function was measured. RESULTS: Mice inoculated with attenuated mengovirus, compared with those inoculated with vehicle or UV-inactivated virus, shed infectious virus for 5 days, had peribronchiolar, perivascular, and alveolar cellular infiltrates, had significantly elevated (p < 0.05) levels of BAL neutrophils, neutrophil chemoattractant CXCR2 ligands (CXCL1, CXCL2, CXCL5), other chemokines/cytokines upregulated during rhinovirus infections (CXCL10, CCL2, and interferon-α, -β, and -λ), and exhibited significant increases (p < 0.05) in BAL fluid myeloperoxidase levels and wet-dry lung weight ratios, indicating neutrophil activation and airway injury, respectively. In these healthy mice, there were no virus-related changes in pulmonary function, consistent with experimental rhinovirus inoculations in healthy humans. CONCLUSIONS: Attenuated mengovirus caused respiratory infections in mice with several days of viral shedding accompanied by lower airway neutrophilic inflammation. These features suggest that this model will be useful for defining mechanisms of rhinovirus-induced airway inflammation in humans.