AbstractTo achieve gene delivery to sensory neurons of the trigeminal ganglion, thymidine kinase‐negative (TK−) herpes simplex viruses (HSV) containing the reporter genelacZ(the gene forE. coliβ‐galactosidase) downstream of viral (in vectors RH116 andtkLTRZ1) or mammalian (in vector NSE‐lacZ‐tk) promoters were inoculated onto mouse cornea and snout.Trigeminal ganglia were removed 4, 14, 30, and 60 days after inoculation with vectors and histochemically processed with 5‐bromo‐4‐chloro‐3 indolyl‐beta‐galactoside (X‐Gal). With vectortkLTRZ1, large numbers of labeled neurons were observed in rostromedial and central trigeminal ganglion at 4 days after inoculation. A gradual decline in the number of labeled neurons was observed with this vector at subsequent time points. With vectors RH116 and NSE‐lacZ‐tk, smaller numbers of labeled neurons were seen at 4 days following inoculation than were observed with vectortkLTRZ1. No labeled neurons could be observed at 14 days after inoculation with vectors RH116 and NSE‐lacZ‐tk.Immunocytochemistry forE. coliβ‐galactosidase and in situ hybridization to HSV latency‐associated transcripts revealed labeled neurons in regions of the trigeminal ganglion similar to that observed with X‐Gal staining. A comparable distribution of labeled neurons in trigeminal ganglion was also observed after application of the retrograde tracer Fluoro‐Gold to mouse cornea and snout.These data provide evidence that retrogradely transported tk−herpes virus vectors can be used to deliver a functional gene to sensory neurons in vivo in an anatomically