The restricted pattern of neurodegeneration seen in Parkinson's disease, and the identification of trophic factors that prevent toxin-induced degeneration of dopaminergic neurons, has spurred research into potential gene therapy for this disease. Herpes simplex virus (HSV-1) is a neurotrophic virus which naturally establishes latency in neurons. HSV-based vectors have been demonstrated to transfer and transiently express transgenes in neurons in brain in vivo. Recent experiments have shown that deletion of multiple immediately HSV genes reduces the potential cytotoxicity of these vectors, and in addition results in altered patterns of transgene expression that may allow for longterm expression required for human gene therapy applications. (C) 1997 Academic Press.