Embryonic rat sympathetic neurons undergo programmed cell death upon NGF deprivation. We show that during postnatal development, these neurons acquire the ability to be supported in vitro by LIF and CNTF as well as NGF. LIF and CNTF do not promote the long-term survival of embryonic day 21 sympathetic neurons in vitro. However, after 5 days of culture in the presence of NGF, the majority of embryonic day 21 sympathetic neurons can be supported by either of these factors. Furthermore, postnatal day 6 sympathetic neurons can be immediately supported by LIF and CNTF, indicating that acquisition of survival responsiveness occurs in vivo as well as in vitro. During this period, neuronal expression of LIF and CNTF receptor mRNAs remains constant, suggesting that sympathetic neurons alter their responsiveness to LIF and CNTF by allowing additional intracellular signaling pathways to promote survival.