Laboratory animal models are important tools for the identification of avirulent herpes simplex virus type 1 (HSV-1) strains which have potential for use in humans as vaccine strains or gene therapy vectors. We have studied an HSV-1 17+ variant, 1716, that has a deletion in the gamma 34.5 gene and which replicates poorly in the footpads of mice and is unable to grow in the mouse central nervous system or dorsal root ganglia (DRG) of the peripheral nervous system following peripheral inoculation. However, 1716 is known to be capable of establishing latent infections in the DRG of mice. Here we show that 1716 is avirulent after ocular infection and has low virulence after intracranial inoculation in SCID mice. Since SCID mice are much more sensitive to HSV-1 infection than immunocompetent mice, our results clearly demonstrate the drastically reduced virulence of the variant 1716 and provide additional support for the hypothesis that this variant would be avirulent in humans.