Drusen-like changes In Bruch's membrane following subretlnal Injection of vitreous In the rabbit were studied by electron microscopy. A sequence of changes Is seen that closely panel lets those observed during drusen formation In primates. The Initial event Is the budding of retinal pigment epithelial (RPE) cells Into Bruch's membrane; the buds, which contain cytoplasm and plasma membrane, are connected to the cytoplasm of the parent RPE cell. Most buds are surrounded by basement membrane, but some penetrate RPE basement membrane Into Bruch's membrane. Later, RPE buds completely separate from the parent RPE cell and show degeneration and disintegration. Finally, drusen-like material, Including vesicular, granular, tubular and linear structures. Is dispersed from the bud remnant Into Bruch's membrane. The study described herein thus supports the hypothesis that drusen are the result of budding from the RPE.