Epileptic seizures in the mature nervous system are associated with axonal sprouting of the hippocampal dentate granule cells and pathological synapse formation. The molecular basis of this morphological rearrangement is obscure. Since epileptic seizures induce the transcriptional activation of genes encoding diverse neurotrophic and growth factors in the dentate granule cells and their targets, morphoregulatory effects of these proteins may contribute to this morphological rearrangement. To determine whether neurotrophins or growth factors exert morphoregulatory effects on dentate gyrus neurons, quite homogeneous preparations of these neurons from postnatal rats were established in primary culture at low density in defined media. Dendrites were distinguished from axons by phase contrast appearance together with microtubule-associated protein-2 immunocytochemistry. Multiple factors enhanced branching of axons but not dendrites of these neurons. The rank order of effectiveness was: basic fibroblast growth factor > brain-derived growth factor > neurotrophin-4 > neurotrophin-3; nerve growth factor was ineffective. No additives of synergistic effects were detected. These results are consistent with the idea that activity-driven expression of these genes contributes to the axonal sprouting and pathological synapse formation evident in diverse forms of epilepsy.