How neurons convert the presence of factors at their axon terminals into signals that affect mechanisms in their cell bodies is unknown, but retrograde axonal transport of the factors themselves may be involved. Nerve growth factor (NGF) and leukemia inhibitory factor (LIF) have previously been shown to produce changes in cell bodies of sympathetic neurons when applied to their peripheral neurites, and it is well established that NGF is retrogradely transported along sympathetic axons. In this study we show that 125I-LIF applied to terminal neurites of rat sympathetic neurons in compartmented cultures is retrogradely transported, but at a much lower level compared to the retrograde transport of 125I-NGF. Transport of 125I-LIF was competed by cotreatment with unlabeled LIF and was blocked by cotreatment with dinitrophenol. The rate of 125I-LIF transport was independent of NGF concentration. However, both 125I-LIF and 125I-NGF transport was reduced by pretreating neurons with LIF. SDS-PAGE analysis showed that retrogradely transported radiolabel which accumulated in cell body-containing extracts following transport of both 125I-LIF and 125I-NGF consisted of intact as well as partially processed species. Radiolabel also accumulated in the medium bathing the cell bodies and migrated near the dye front on SDS-PAGE, implying that both factors were extensively degraded and released by the neurons. These results are consistent with the suggestion that the retrograde transport of LIF, as thought for NGF, may be important for retrograde signaling mechanisms.