Normally, human retinal pigment epithelial (RPE) cells in confluent monolayers maintain a hexagonal to oval shape. However, when these monolayers were overlaid with autologous vitreous, the RPE cells elongated and migrated into the vitreous gel as bipolar fibrocytelike cells. We studied the effect of sodium hyaluronate and collagen individually. Retinal pigment epithelial cells overlaid with hyaluronate did not change their morphologic features. In contrast, when RPE monolayers were overlaid with a collagen gel, the cells changed from their normal epithelial characteristics to bipolar fibrocytelike cells that later migrated into the collagen gel. Exposure of RPE cells to vitreous may play a role in the pathogenesis of proliferative vitreoretinopathy.