My project aimed at finding the most accurate way to determine if someone is infected with HSV-2 in humans, and if serology is an accurate indicator of infection in those who are vaccinated. Combinations of infection markers in guinea pigs that can be measured in humans (serology, genital lesions, viral shedding of HSV DNA) were compared to the "gold standard" (most accurate assessment of infection) which include genital lesions, viral shedding of HSV DNA, day 2 & 4 vaginal viral titers post infection and HSV DNA in dorsal root ganglia (DRG). This allowed us to help determine the most accurate combination of infection markers to measure HSV infection in human vaccine trials. Furthermore, this led to the conclusion that including serology as a criteria of infection leads to many false positive and false negative results in those who are vaccinated.