Various growth factors and their receptors are present in the nervous system. This review focuses on the presence of epidermal growth factor (EGF) and its receptors in the central nervous system (CNS). Evidence indicates that EGF in the CNS is the result of local synthesis, by intrinsic and blood-derived macrophages, glial cells and neurons, and uptake from the peripheral blood through the circumventricular organs and probably also through the blood-brain barrier. Evidence is accumulating suggesting that EGF regulates a variety of CNS functions in a specific manner. EGF influences CNS growth, differentiation and maintenance (actions proposed to promote neural regeneration and cell survival following a variety of insults). EGF also induces neuromodulatory actions, affects the neuroendocrine system, and suppresses food intake and gastric acid secretion. Acute and chronic pathological processes, e.g., various cancers, stimulate the production and release of EGF in various cell systems. Monitoring of EGF by the CNS may participate in several neurological manifestations (e.g., appetite suppression, neuroendocrine alterations) frequently accompanying acute and chronic disease. EGF and transforming growth factor-alpha (TGF-alpha, a factor that binds to the EGF receptor with high affinity and induces the same biological signals as EGF) also may be involved in the promotion of malignancy in the CNS and in the neuropathogenesis of degenerative disorders. Thus evidence is accumulating concerning the neurophysiological or neuropathophysiological significance of EGF in the nervous system.