Determination of neurotransmitter phenotype in the peripheral nervous system (PNS) has been intensively characterized. However, relatively little is known about the underlying molecular and biochemical events involved in determination of transmitter phenotype in the central nervous system (CNS). It has been well established that nerve growth factors regulate cell growth and differentiation. They are increasingly recognized as playing an important role in many decision-making steps during development. Published data suggest that neurotransmitter phenotype is determined largely by exogenous stimuli, such as nerve growth factors--acidic/basic fibroblast growth factor, epidermal growth factor, neurotrophins, etc., working in concert with the genetic programmes. They exert potent effects independently or synergistically with other molecules by acting either on neural precursor cells or differentiated neuronal cells. However, the process of transmitter phenotype determination in the CNS is only beginning to be understood, with more uncharacterized substances, with considerable potency in this respect being reported and in need of isolation and further study. These studies will bring great advances in our existing knowledge of brain development and have potential value for the development of new treatments for neurodegenerative diseases.