The role of M1 and M2 macrophages (derived in a type 1, respectively in a type 2 cytokine milieu) in human rhinovirus (HRV) infections is not known. M2 macrophage numbers are believed to be increased in asthma and could play a role in the increased susceptibility to HRV-infections. We hypothesized that upon HRV infection M2 produce less innate interferons (IFN-α/β/λ) as compared to M1 macrophages. Methods. Monocyte-derived macrophages (MDM) obtained from PBMC were polarized to M2 (by treatment with IL-4) and to M1 (by treatment with IFN-γ&TNF-α) and infected with HRV16. IFN-α/β/λ gene expression was measured by RT-PCR and protein levels by ELISA. Supernatants of HRV16-infected M1& M2 and MDM were titrated on Hela-Ohio cells to ascertain their 50% tissue culture infective dose TCID50/ml. Results. Upon HRV16 infection we found increased IFN-α1, -β and -λ1 gene expression at 8h and IFN-α1 and -λ1 gene expression at 24 h in M1 as compared to M2 macrophages and MDM. Increased production of IFN-β and -λ1 at 8h and for IFN-α, -β and -λ1 at 24 h, 48 h and 72 h was observed in HRV16-infected M1 as compared to M2 macrophages and MDM. Rhinovirus titer was decreased in M1 macrophages. In conclusion, M1 macrophages produce high levels of antiviral IFN-α/β/λ1 and consequently are less susceptible to virus infection. In contrast M2 macrophages produce low levels of IFN-α/β/λ and this could play a role in virus-induced exacerbations of asthma.