The generation of neurons and glia in the developing nervous system is likely to be regulated by extrinsic factors, including growth factors and neurotransmitters. Evidence from in vivo and/or in vitro systems indicates that basic fibroblast growth factor, transforming growth factor (TGF)-alpha, insulin-like growth factor-1, and the monoamine neurotransmitters act to increase proliferation of neural precursors. Conversely, glutamate, gamma-aminobutyric acid, and opioid peptides are likely to play a role in down-regulating proliferation in the developing nervous system. Several other factors, including the neuropeptides vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide, as well as the growth factors platelet-derived growth factor, ciliary neurotrophic factor, and members of the TGF-beta family, have different effects on proliferation and differentiation depending on the system examined. Expression of many of these factors and their receptors in germinal regions of the central nervous system suggests that they can act directly on precursor populations to control their proliferation. Together, the findings discussed here indicate that proliferation and cell fate determination in the developing brain are regulated extrinsically by complex interactions between a relatively large number of growth factors and neurotransmitters.