BACKGROUND--Variation of fluorescence derived from lipofuscin in the retinal pigment epithelium has been recorded with age and in retinal diseases. Studies have been based largely on in vitro observations on eye bank eyes which has placed severe limitations on the data available. METHODS--A technique is described whereby in vivo imaging of autofluorescence of the fundus was achieved using a scanning laser ophthalmoscope. RESULTS--The optical characteristics, distribution, and variation with disease imply that the fluorescence is derived from lipofuscin in the pigment epithelium. Autofluorescence is shown to be abnormally high in certain inherited diseases, and low in the presence of retinal atrophy. CONCLUSION--This technique may be useful both in clinical practice and research. It may allow the detection of the abnormal phenotype in genetically determined disease at a time when other techniques may not. Longitudinal studies of age related macular disease would permit correlation between changes in the pigment epithelium and Bruch's membrane to be established.