The effect on nasal epithelial cells in monolayer cultures of infection with rhinovirus, coronavirus 229E, influenza type A, and adenovirus was studied. Fragments (1 x 2 mm) of epithelium with adherent submucosa from nasal polyps, adenoids, or nasal turbinates were cultured in plastic dishes with media containing a serum supplement. Within a week a monolayer of epithelial cells with interspersed ciliated cells surrounded each fragment. Epithelial monolayers were exposed to 10(3) to 10(4) TCID50/ml of each virus; unattached virus was removed after 3 h. Replication of virus was examined by doing viral titrations of the media daily, and ciliated and nonciliated epithelial cells in the monolayer were examined morphologically with an inverted microscope. The peak titer of rhinovirus and coronavirus occurred 24 to 48 h after inoculation, indicating that viral replication was occurring. However, no detectable damage or cytopathic effect (CPE) developed in the monolayer of epithelial cells when compared with that in uninfected control cells. In contrast, infection of epithelial monolayers with influenza or adenovirus resulted in CPE and destruction of the monolayer. The marked difference in the effect of these respiratory viruses on nasal epithelial cells may reflect similar differences in their effect on respiratory tract mucosa in the intact host. If so, the pathogenesis of symptom production during rhinovirus and coronavirus infections must be by mechanisms other than destruction of the nasal lining.