Small, experimental, non-rhegmatogenous retinal detachments (blebs) in rabbit eyes resorbed 50% more slowly when filled with autologous serum than with Hanks' solution. To study the fate of large molecules in the subretinal space, carboxyfluorescein and several sizes of FITC-dextrans were injected into blebs and their movement followed by fluorophotometry. Carboxyfluorescein diffused quickly into the vitreous and was gone from the space after 8 hr. FITC-dextran 10-S (smaller than albumin) also diffused readily into the vitreous and took about 30 hr to be eliminated from the subretinal space. The diffusion of FITC-dextran 70-S and 150-S (both larger than albumin) was markedly slower, and roughly 80% of the 150-S was still present in the subretinal space after 3 days. Since the subretinal fluid in all of these blebs resorbed within 10 hr, the physiologic mechanisms for fluid resorption and elimination of large substances appear to be independent. Damaging the RPE barrier with sodium iodate allowed even the larger FITC-dextrans to exit from the subretinal space.