OBJECTIVE: The objective of this study was to estimate herpes simplex virus-2 (HSV-2) seroprevalence from a weighted sample of adults attending relatively affluent, suburban primary care physician (PCP) offices. GOAL: Many PCPs in relatively affluent areas do not believe national estimates of HSV-2 seroprevalence are representative of their patient populations. This study aimed to measure HSV-2 seroprevalence in these patient populations. STUDY DESIGN: We conducted a cross-sectional study with approximately 5400 individuals aged 18 to 59 years. Individuals were recruited at 36 PCP offices in 6 U.S. cities and tested for HSV-2 using Focus enzyme-linked immunosorbent assay. A computer-assisted questionnaire was used to assess risk behaviors associated with genital herpes. RESULTS: Among 5452 individuals who provided an analyzable blood sample, the overall weighted HSV-2 seroprevalence was 25.5% (95% confidence interval, 20.2-30.8%). Only 11.9% of HSV-2-seropositive patients reported a history of genital herpes. CONCLUSIONS: Results illustrate the need for greater suburban PCP and patient awareness of the high HSV-2 seroprevalence in this setting.