A reproducible neuronal degeneration induced by nerve lesion in neonatal rats or mice provides a convenient in vivo assay for testing the survival-promoting activity of putative growth factors on motoneurons. The goal of this study was to compare the rescue effects of the four known neurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4)] and two of the cytokines [ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF)] in one particular experimental model of spinal motoneuron degeneration at two different survival times. The sciatic nerve was cut in neonatal rats and the factors were applied onto the nerve stump; bovine serum albumin was used in controls. Simultaneous application of the retrograde tracer fluoro-gold made it possible to count motoneurons specifically in the sciatic pool. One week after lesion, the neurotrophins BDNF, NT-3 and NT-4, but not NGF, equally enhanced motoneuron survival compared to controls; their effects were significantly better than those of the cytokines. However, the rescue from cell death was only transitory because a great number of the motoneurons died during the second week after nerve lesion. Additional BDNF and/or CNTF supplied by repeated subcutaneous injections (1 mg/ml) over 2 weeks could not prevent this delayed motoneuron loss. These results suggest that still other factors or alternative routes of administration may be required for permanent rescue of the lesioned immature motoneurons.