Recent progress has revealed similarities between the receptors and signaling systems used by neurotrophic factors as compared to other growth factors and cytokines. The neurotrophins use a family of receptor tyrosine kinases known as the Trk receptors, whereas ciliary neurotrophic factor (CNTF) uses a "cytokine receptor" system that shares receptor components with a number of distantly related cytokines. We have used a human embryonal carcinoma cell line and human leukemia cell lines to examine the actions of the neurotrophins and CNTF on cellular differentiation. Our findings demonstrate that specific combinations of neurotrophic factors are required to influence the neuronal progenitor cells to become postmitotic mature CNS neurons. Such synergistic interactions may play an important role in modulating the differentiation of a wide assortment of neuronal precursors in the developing nervous system. Furthermore, our studies with leukemia cells suggest that neurotrophic factors may play a similar role in hematopoietic differentiation and that these factors may have therapeutic application in leukemia differentiation.