Cerebellar granule cells offer a useful model system to study the effects of neurotrophins during development. We have used a defective herpes simplex virus type 1 (HSV-1) vector containing brain-derived neurotrophic factor (BDNF) to express this neurotrophin in aggregate cultures of granule cells. Viral infection led to easily detectable BDNF expression and neurite outgrowth of granule cells, expressing the high affinity receptor TrkB. Neurite elongation mediated by the HSV-1 vector producing BDNF was similar to that found after exposure to purified BDNF. This study demonstrates the efficacy of HSV-1 vectors for delivery and expression of neurotrophins in cerebellar granule cells. The biological responses measured indicate the effectiveness of HSV-1 vectors as potential therapeutic tools.