Detection of infectious virus and viral antigen from selected sites in the nose was done in 20 volunteers with experimental rhinovirus colds and in 10 sham inoculated controls. For five days after virus inoculation, repeated samples were collected both by swabbing the nose and pharynx and by epithelial biopsy of localized areas in the nose with a sheltered cytology brush. All samples were cultured for virus. Cells in the biopsy specimens were examined with immunoperoxidase staining for detection of rhinovirus antigen in epithelial cells. Not all parts of the nasal lining were infected. While 60% of the nose/throat swabs samples were positive by culture, only 32% of the brush biopsies were positive. With the biopsy specimens, the number of positive cultures was lower in the anterior part of the nose (nasal septum) than in the middle part of the cavity (turbinates), and there was a tendency for an increased number of sites to become positive during the course of the illness. Eight (16%) of 51 specimens from infected volunteers had rhinovirus antigen detected in ciliated epithelial cells. These findings indicate that the entire nasal epithelium is not infected at the time of peak symptoms during experimental rhinovirus colds.