Background and objective: Infection with rhinovirus (RV) is the most common trigger for acute asthma and COPD. The aim of this study was to characterize the variability in the response of primary bronchial epithelial cells to infection with several strains of RV. Methods: RV strains, RV-43, RV-48 (major group RV), RV-47 (minor) and EV-68 (enterovirus), were cultured from subjects with acute asthma and compared with the laboratory RV strains, RV-16, RV-14 (major) and RV-1B (minor). Primary bronchial epithelial cells were obtained from healthy control and asthmatic subjects by endobronchial brushing. Response to infection was assessed by the release of IL-6, interferon (IFN)-γ induced protein (IP)-10 and IFN-β, as measured by ELISA. Viral replication was assessed by serial titration assays and cell viability by flow cytometry. Results: Major group RV strains and EV-68 all efficiently infected and replicated in epithelial cells causing little cell death. The clinical major group RV strains caused greater release of IL-6 and IP-10 compared with laboratory major group RV strains. Infection with minor group RV resulted in greater release of IP-10, IL-6 and IFN-β that was associated with induction of apoptosis and less efficient viral replication. Asthmatic bronchial epithelial cells were less able to respond by releasing IFN-β following infection with RV-1B. Conclusions: Considerable diversity exists in the response to RV strains, especially between minor and major group RV. The impaired IFN-β response in asthmatic bronchial epithelial cells may make them particularly susceptible to minor group RV.