Fluorescence bronchoscopy with a ratio fluorometer probe was used to examine patients with known or suspected bronchogenic carcinoma to determine if early lung cancer can be detected with low dose Photofrin II without skin photosensitivity. Seventeen patients were examined 24 hours after injection of 0.25 mg/kg Photofrin II. Using a red-green (R/G) ratio of greater than 1.5 times the mean value of normal areas as being potentially significant, both carcinoma in situ and invasive cancers were accurately localized (sensitivity 100% specificity 61%). The majority of the false positive fluorescence (80%) came from the lesions with dysplasia. The elevated R/G ratios from the cancerous and pre-cancerous lesions were found to be due to a significantly lower green autofluorescence. No skin photosensitivity was observed on all seventeen patients. Ratio fluorometry was also carried out in thirty-one patients with known or suspected lung cancer without Photofrin II. A similar diagnostic accuracy was found (sensitivity 90%, specificity 86%). Our results suggest that early lung cancer may be detectable by ratio fluorometry by exploiting autofluorescence differences between tumor and normal tissues.