Spinal cord neurons in the intermediolateral column (IML) that innervate the adrenal medulla require target-derived factor(s) for their maintenance in vivo. Selective destruction of the adult rat adrenal medulla causes an approximate 25% loss of Nissl-stained IML neurons between spinal cord levels Th 4 weeks after surgery. We have previously suggested that basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) or closely related molecules are present in adrenal chromaffin cells and granules. Basic FGF supplemented in gelfoams to the medullectomized adrenal gland fully prevented IML neuron losses. These results are now extended by demonstrating that (i) CNTF administered in vivo (7.2 micrograms/gelfoam) also rescues IML neurons, and (ii) the rescue effect is abolished by splanchnicotomy, i.e. interruption of axonal pathway from the spinal cord to the adrenal gland. These data would be consistent with CNTF being a retrograde trophic messenger to the spinal cord, but do not exclude the possibility that CNTF mimics or induces the formation of an endogenous trophic factor.