Both target-derived and injury-induced factors could be involved in the axotomy-induced increases in galanin expression in dorsal root, ganglion (DRG) neurons. Galanin mRNA levels were studied in primary cultures of E13.5 embryos, grown for 14 days in culture, in response to two candidate molecules, nerve growth factor (NGF) and leukemia inhibitory factor (LIF). In these cultures, NGF withdrawal alone resulted in a significant increase in galanin mRNA. Addition of LIF onto NGF-containing cultures did not produce a significant increase, while addition of LIF to NGF-deprived cultures caused an upregulation of galanin mRNA which was significantly stronger than that of NGF withdrawal alone. Thus, NGF withdrawal and LIF increase act together to up-regulate galanin gene transcription in DRG neurons.