Insulin receptor processing in human erythrocytes was investigated. Insulin binding to the cell surface was found to decrease by 70% in cells which had first been incubated with insulin for 3 h, then washed for 3 h. After an additional 16-h incubation without insulin, the level of cell surface insulin binding was restored to control values, even in the presence of cyclohexamide. Our results suggest that erythrocyte insulin receptors are internalized in response to insulin and that receptors are subsequently recycled to the surface of the cell.