Endoscopic screening for sporadic colorectal cancer relies in part on the detection of adenomatous polyps. Nonpolypoid adenomas or flat dysplasia may go unrecognized by conventional endoscopy. This study attempted to develop and test a novel endoscopic method for detecting polypoid and nonpolypoid colonic adenomas. Colectomy specimens from 3 patients with familial adenomatous polyposis containing polypoid and nonpolypoid adenomas were illuminated with excitation light at 351 and 364 nm. Endoscopic images of the net tissue fluorescence emitted were collected over the spectral bandwidth from 400 to 700 nm. Each raw image was corrected for differences in distance and instrument light collection efficiency by normalizing to a spatially averaged image. Intensity thresholding was then used to identity regions of diseased mucosa. The average fluorescence intensity from normal mucosa was found to be greater than that from adenomas by a factor of 2.2 +/- 0.6. The sensitivity and specificity for detecting a region of dysplasia varied with the threshold value selected. At a threshold of 75% of the average normal intensity, a sensitivity of 90% and a specificity of 92% were achieved. Fluorescence images of colonic mucosa can be collected endoscopically, and dysplasia can be detected and localized with high sensitivity and specificity. These results show the potential of this technique to direct endoscopic biopsy.