We compared neuroinvasive properties of HSV-1 MacIntyre strain and HSV-2 G strain, after inoculation of mice by intraperitoneal, intranasal and intracaudal route, by scoring for encephalitis and death. HSV-2 was more neuroinvasive than HSV-1 by any route, since mice inoculated intranasally or intracaudally with HSV-2 required 100 fold lower dose than HSV-1 to induce encephalitis and death, which occurred earlier than in HSV-1 infected mice. HSV-2 was found in brain tissues at a lower concentration (10(1.8) to 10(2.7) PFU per 0.1 g of brain) than HSV-1. Mice inoculated with HSV-2 developed a more aggressive behavior than those inoculated with HSV-1, although they showed a lower virus concentration per gram of brain. These results showed that HSV-2 G strain was more neuroinvasive than HSV-1 MacIntyre strain and its ability to produce damage of CNS was not directly related to the amount of virus in it, and suggests that neuroinvasiveness is a complex phenomenon, which could involve viral genomic expression and evasion of the immune system.