A need exists in respiratory medicine for a technology capable of identifying airway pathology on a micron scale. This study has demonstrated the feasibility of optical coherence tomography (OCT) for ultrahigh resolution imaging of the upper respiratory tract by in vitro studies of human tissue. OCT is a relatively new technique that can be used to noninvasively collect tomographic images of tissue microstructure with micron-scale resolution. OCT is analogous to ultrasound, measuring the intensity of infrared light rather than acoustical waves. Samples throughout the upper respiratory tract, from the epiglottis to the secondary bronchi, were imaged. The resulting images were compared with histopathology and verified the ability of OCT to delineate relevant structures such as the epithelium, mucosa, cartilage and its sublayers, and glands at a resolution higher than any clinical imaging technology. The ability of OCT to generate image resolution in the range close to that of histopathology in real time, as well as easy integration with small, relatively inexpensive endoscopes, low cost, and lack of a need for a transducing medium, supports the hypothesis that this optical technology could become a powerful modality in the diagnosis and management of a wide range of clinical respiratory pathology.