Herpes simplex virus type 2 (HSV-2) is the most prevalent sexually transmitted pathogen worldwide. There is considerable biological and epidemiological evidence that HSV-2 infection increases the risk of acquiring HIV infection and may also increase the risk of transmitting HIV. Here, we use a mathematical model to predict the effect of a high-prevalence HSV-2 epidemic on HIV incidence. Our results show that HSV-2 epidemics can more than double the peak HIV incidence; that the biological heterogeneity in susceptibility and transmission induced by an HSV-2 epidemic causes HIV incidence to rise, fall, and then rise again; and that HSV-2 epidemics concentrate HIV epidemics, creating a "core group" of HIV transmitters. Our modeling results imply that findings from HSV-2 intervention trials aimed at reduction of HIV incidence will be variable and that positive findings will be obtained only from trials in communities in which HIV incidence is steeply rising.