Somatic cell hybrids between rat XC(HPRT-) cells, non-permissive for herpes simplex virus type 1 (HSV-1) infection, and permissive mouse L(TK-) cells were constructed and karyotyped. Infection of these hybrid cells by HSV-1 strains F and MP revealed that they were susceptible to the virus. The amounts of virus produced by the hybrid cells, as well as the cytopathic effect observed, was very similar to that of the parental L(TK-) cells. Our results suggest that failure of HSV-1 to replicate in XC cells is more likely to be due to the absence of cellular elements required for efficient virus multiplication rather than to the presence of blocking or inhibiting factors.