In low-density, serum-free cultures of neurons from embryonic rat dorsal root ganglia, interleukin-6 supports the survival of less than one third of the neurons yet virtually all of them bear interleukin-6 α-receptors. A finding that might explain this selectivity is that interleukin-6 acts on sensory neurons in culture through a mechanism requiring endogenous brain-derived neurotrophic factor. Antibodies or a trkB fusion protein that block the biological activity of brain-derived neurotrophic factor synthesized by dorsal root ganglion neurons also block the survival-promoting actions of interleukin-6 on these neurons. Two results indicate that interleukin-6 influences synthesis of brain-derived neurotrophic factor in adult dorsal root ganglion neurons. Intrathecal infusion of interleukin-6 in rats increases the concentration of brain-derived neurotrophic factor mRNA in rat lumbar dorsal root ganglia. The induction of brain-derived neurotrophic factor in dorsal root ganglion neurons that is seen after nerve injury in rats or wild-type mice is severely attenuated in mice with null mutation of the interleukin-6 gene. In brief, the ability of interleukin-6 to support the survival of embryonic sensory neurons in vitro depends upon the presence of endogenous brain-derived neurotrophic factor and the induction of brain-derived neurotrophic factor in injured adult sensory neurons depends upon the presence of endogenous interleukin-6.