It was previously reported that administration of cadmium (Cd) to CBA mice latently infected with herpes simplex virus (HSV) results in a high incidence of virus reactivation in vivo. In the present study, Cd-inducible reactivation was used to compare CBA with four other laboratory mouse strains. HSV reactivation, as measured by the recovery of infectious particles from latently infected trigeminal ganglia following Cd treatment, occurred predominantly in the CBA strain and was almost entirely absent from other strains tested. There was no correlation of strain-dependent Cd toxicity with the recovery of infectious virus. In situ examination of Cd-treated ganglia from latently infected CBA and BALB/c mice revealed that viral antigens were expressed exclusively in CBA specimens, but that viral replicative transcripts were expressed in both strains, although more strongly in CBA than in BALB/c specimens. We conclude that Cd treatment had induced reactivation of HSV from both mouse strains, and that the reactivation process was completed in CBA but not in BALB/c mice.