To develop an antiviral drug, it is extremely important to have a relevant cell culture model system. The airway epithelial cells lining the conductive airways are the primary target for all three classes of rhinoviruses. However, rhinovirus replication is not very robust in airway epithelial cells; therefore, it does not cause cytopathic effects. However, rhinovirus induces replication-dependent cytokines such as type I and type III interferons and CXCL-10, which can be used as surrogates for viral load. Here, we describe a method using the immortalized normal human bronchial epithelial cell line, BEAS-2B cells. These cells readily grow in serum-free medium and can be infected with rhinovirus A and B. The binding, endocytosis, and replication of the virus induce CXCL-8 in these cells. These cells also respond to replicating virus by showing robust CXCL-10 production. Both CXCL-8 and CXCL-10 secreted into the medium can be readily measured by ELISA. Therefore, this method can be used to examine the drugs that can inhibit binding, endocytosis, and replication of the virus.