Brain-derived neurotrophic factor (BDNF) promotes neuronal cell survival and differentiation in the central nervous system. BDNF mRNA is expressed at high levels in hippocampus and BDNF serves as a trophic factor in primary cultures of rat hippocampus. A hippocampal stem cell line HIB5, which is immortalized by the temperature sensitive SV 40 T antigen, undergoes neuronal differentiation at non-permissive temperatures. During the differentiation process, platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) facilitate cell survival and differentiation in HiB5 cells as well as in primary cultures of rat embryonic hippocampal cells. This report demonstrates that HiB5 cells express a functionally active PDGF beta receptor and that PDGF and bFGF stimulate the expression of BDNF within 2 h. These results propose that BDNF is a candidate mediator of trophic effects of PDGF and bFGF in the hippocampal stem cell line HiB5.