BACKGROUND: This study investigates socio-economic differentials in herpes simplex virus type 2 (HSV-2) seroprevalence in Australian men and women using individual and geographic measures of socio-economic status. METHODS: HSV-2 seropositivity among men and women aged over 25 years was investigated by levels of individual and area-based measures of socio-economic status (SES) in a series of Poisson regression models, variously adjusting for age, country of birth, marital status, indigenous status, and urban/rural residence as potential confounders. Serum and socio-demographics were collected during 1999 and 2000 in a population-based Australia-wide prevalence survey. RESULTS: HSV-2 seroprevalence was significantly lower in areas of low SES than in high SES areas among both men (P for trend <0.001) and women (P for trend = 0.004) for all ages. A similar pattern was evident for individual education level for men with lower rates of HSV-2 in respondents with lower educational achievement (relative risk = 0.77, 95% CI 0.61-0.97, P = 0.024). In contrast, HSV-2 prevalence was higher for women with lower individual levels of education for all ages (relative risk = 1.22, 95% CI 1.04-1.44, P = 0.017). Analyses stratifying HSV-2 prevalence for individual education level by area-based SES showed the highest prevalence of HSV-2 in women with the lowest education level residing in the highest SES areas. This pattern was not evident in men, with a greater concordance between individual and area-based SES. CONCLUSION: HSV-2 seroprevalence is not consistently distributed across individual and area measures of SES, suggesting that upward and downward mixing between social strata in men and women is an important mode of HSV-2 transmission.