The potent mitogen epidermal growth factor (EGF) binds to specific receptors on human fibroblasts. In the present study we have used a quantitative EM autoradiographic approach to visualize the events involved in the binding process. When 125I-EGF is incubated at 4 degrees C for 120 min, labeled EGF primarily localizes to the plasma membrane of the fibroblast but when incubated at 37 degrees C for 120 min., over 2/3 of the labeled material is internalized by the cell. The internalized radioacitivity is primarily localized to lysomes. These studies demonstrate a temperature-dependent internalization of EGF following initial binding to specific plasma membrane receptors.