Epidermal growth factor (EGF) is a mitogen for epidermal cells in vivo1,2 and for a wide variety of cells in culture3–5. Recently, we and others have reported that EGF can also regulate the cellular levels of various hormones6 and fibronectin7 at concentrations which only minimally influence cell division. In addition, EGF treatment of GH3 cells affects chromatin structure such that isolated nuclei from treated cells have an increased capacity to bind bacterial RNA polymerase in initiation site complexes6. Thus, the data suggest that various nuclear functions are modulated by EGF in GH3 cells despite its failure to affect DNA synthesis or cell proliferation. Recently, Yanker and Shooter8 have reported on the nuclear accumulation of nerve growth factor (NGF) in PC12 cells in which NGF does not promote cell division but does influence RNA and protein synthesis while inducing overt differentiation (neurite outgrowth). The similarities between the two systems and the various theories regarding the mechanism by which mitogens exert their growth-promoting and other effects9,10 led us to investigate whether an interaction between EGF and the cell nucleus can be demonstrated after surface binding and internalization of EGF in GH3 cells. We report here that when its lysosomal degradation is inhibited by chloroquine, EGF accumulates in the nucleus.