Fifty-two eyes with drusen of the optic nerve head from the autopsy and surgical files of the Eye Pathology Laboratory of the Wilmer Institute from January 1967 through December 1975 were reviewed, and histochemical and electron microscopic studies performed. Histopathologic associations with the drusen included 19 eyes with associated optic nerve atrophy, 16 eyes with peripapillary crowding, one case involving prominent dilated vessels pushed aside by the drusen, and one eye with central retinal vein occlusion. Drusen appear to be composed predominantly of a mucoprotein matrix with significant quantities of acid mucopolysaccharides along with small quantities of ribonucleic acid and, occasionally, iron. The literature is reviewed and various correlations and pathogenetic theories are discussed.