BACKGROUND: Herpes simplex virus (HSV) type 2 increases the risk of human immunodeficiency virus (HIV) infection, and, in regions with high prevalence of both viruses, control of HSV-2 may be an effective method of HIV prevention. Identification of modifiable factors for prevention of HSV-2 infection is essential. We conducted this study among female bar and hotel workers in Moshi, Tanzania. METHODS: Factors associated with prevalent infection were examined among 1039 women. Predictors of incident infection were examined among 360 women initially HSV-2 negative, with at least 1 follow-up visit. RESULTS: HSV-2 prevalence was 56.3% (95% confidence interval [CI], 53.3%-59.3%). Only 2.5% of women able to name a sexually transmitted infection named herpes. Incidence was 14.2 cases/100 person-years (95% CI, 10.5-18.8 cases/100 person-years). Incident HSV-2 infection was independently associated with HIV infection, younger age of sexual initiation, ethnicity, alcohol consumption, and having a male partner with other sexual partners. CONCLUSIONS: The occurrence of HSV-2 is high in this population, but knowledge is low. Development of education programs to increase awareness of HSV-2 is critical. The control of both HSV-2 and HIV infections is a major public health priority in Moshi. Prevention interventions in this and other high prevalence populations might most effectively target younger women, before initiation of sexual activity.