This study is based on the clinico-pathological examination of 512 eyes. As senile macular degeneration developed drusen appeared to alter in consistency and become more fluid. This resulted in a spectrum of clinical appearances classified as hard, semisolid, soft or serous, and regressing. Histologically the hyaline contents of the drusen changed to a pale-staining amorphous material which electron microscopy showed to consist of vesicles. This membranous debris first appeared beneath the pigment epithelium in normal aged eyes but its later accumulation led to a widespread shallow separation of the basement membrane. The softening of drusen was most evident in group IV in which subretinal neovascularization was first detected. At this stage the retinal pigment epithelium also showed its greatest proliferative activity and the formation of abnormal basement membrane material.