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To assess the prevalence and determinants of HIV infection in the general population in Bagalkot district, a largely rural district in the southern Indian state of Karnataka.Approximately 6700 individuals aged 15–49 years were randomly sampled from 10 villages and six towns, from three of Bagalkot's six sub-districts. Each consenting respondent was administered a questionnaire, followed by blood collection and testing for HIV, syphilis, and herpes simplex virus type 2 (HSV-2) on a 25% sub-sample.HIV prevalence was 2.9% overall, 2.4% in urban areas and 3.6% in rural areas [odds ratio (OR), 0.65; 95% confidence interval (CI), 0.45–0.95]. Significant differences in HIV prevalence were seen between the three sub-districts, with prevalences of 1.1, 3.0 and 6.4% (P < 0.05), and HIV prevalence in the 10 villages ranged from 0 to 8.2%. Reported multiple sexual partners, receiving money for sex and a history of medical injections were significantly associated with HIV infection, as were older age, being widowed, divorced, separated or deserted, lower education levels and being a woman of a lower caste. There was a strong association between HSV-2 and HIV infection (OR, 5.2; 95% CI, 2.3–11.5).The rural nature of this epidemic has important implications for prevention and care programs. The striking differentials observed in HIV prevalence between sub-districts and even villages suggest that risk and vulnerability for HIV are highly heterogeneous. Further research is required to understand the individual and community-level factors behind these differentials, so that preventive interventions can be directed to where they are most needed.