The study investigates the binding, internalization, and degradation of 125I-labeled human epidermal growth factor (hEGF) in human fibroblasts. At 37°C, hEGF binds to fibroblasts and is rapidly degraded, with the degradation products being 125I-monooiodotyrosine. At 0°C, hEGF binds but does not degrade. The degradation is blocked by inhibitors of metabolic energy production, proteases, lysosomotropic agents, local anesthetics, and ammonium chloride. After binding and degradation, fibroblasts lose their ability to rebind fresh hEGF, but this capacity can be restored by incubation in a serum-containing medium. The results suggest that hEGF initially binds to the cell surface, is internalized, and then degraded, with the degradation process involving endocytosis and lysosomal activity. The study also examines the role of protein synthesis in the recovery of hEGF binding capacity and the mechanisms by which various agents inhibit hEGF degradation.The study investigates the binding, internalization, and degradation of 125I-labeled human epidermal growth factor (hEGF) in human fibroblasts. At 37°C, hEGF binds to fibroblasts and is rapidly degraded, with the degradation products being 125I-monooiodotyrosine. At 0°C, hEGF binds but does not degrade. The degradation is blocked by inhibitors of metabolic energy production, proteases, lysosomotropic agents, local anesthetics, and ammonium chloride. After binding and degradation, fibroblasts lose their ability to rebind fresh hEGF, but this capacity can be restored by incubation in a serum-containing medium. The results suggest that hEGF initially binds to the cell surface, is internalized, and then degraded, with the degradation process involving endocytosis and lysosomal activity. The study also examines the role of protein synthesis in the recovery of hEGF binding capacity and the mechanisms by which various agents inhibit hEGF degradation.