We have studied the effects of hemicholinium-3 (HC-3), an outer segment and retinal pigment epithelium (RPE) toxin and sodium iodate, an RPE toxin, on retinal and RPE adhesion in rabbits. During the first 3 days after intravitreal HC-3, the force required to peel retina from RPE fell to 50% of normal, and large patches of RPE separated from Bruch's membrane and adhered to the peeled retina. The same phenomena were observed during the first 100 min after intravenous sodium iodate. Beyond 3 days after HC-3, and 100 min after sodium iodate, the peeling force became even weaker, but separation occurred at the subretinal space or by fragmentation of RPE cells. Acute RPE toxicity probably accounts for the initial weakening of the bond between RPE and Bruch's membrane.