Nerve growth factor (NGF) is an insulin-like protein, which regulates growth, development and maintenance of sympathetic and embryonic sensory neurons. It is found in varying amounts in the venom of all tested poisonous snakes and in the male mouse submaxillary gland. Its first interaction with target neurons is the binding to a cell surface receptor. The occurrence of internalized NGF as well as specific nuclear binding sites, however, suggest a mechanism of action not exclusively mediated through cell surface receptors. A model of the overall mechanism of action of NGF accommodating these observations is proposed. NGF has a variety of effects on the central nervous system (CNS) under experimental conditions: It enhances the regeneration of central adrenergic neurons and it brings forth temporal changes in surface specificity of cultured embryonic chick tectal cells. Furthermore, NGF specific binding sites are found in the synaptosomal fraction of homogenates of embryonic chick brain. In the unperturbed brain, however, no definitive role of the growth factor has been found, and the significance of NGF in the CNS is still an open question.