Interleukin 5 (IL-5) has been implicated as a causal mediator in the development of pulmonary eosinophilia and airway hyperreactivity in human asthma. Supportive evidence for a pathogenic role of IL-5 in this disease has been provided by guinea pig models in which antigen-induced lung eosinophilia and bronchial hyperresponsiveness have been specifically attenuated with a neutralizing antibody to IL-5. In the present report, we describe a rapid mechanism-based model of IL-5-induced eosinophilia in the guinea pig. Our results show that intravenous injection of human IL-5 induced a 5-10-fold increase in the percentage and number of eosinophils in blood within 1 hour. In contrast, neutrophils and mononuclear cells were not recruited during this time. The increase in eosinophils was blocked by pretreatment of animals with an anti-IL5 monoclonal antibody (TRFK5) in doses similar to those which inhibit eosinophilia in guinea pig asthma models. Furthermore, dexamethasone, a potent inhibitor of eosinophilia in guinea pig asthma, profoundly suppressed the eosinophilia induced by human IL-5. This rapid model will be useful for elucidating the eosinophil activating properties of IL-5 in vivo and may potentially facilitate the development of IL-5 receptor antagonists for the specific blockade of the eosinophilic inflammation observed in human asthma.