Health care needs of those infected with the human immunodeficiency virus (HIV) and subsequent transmission dynamics are altered by migration after infection. We interviewed 760 HIV-infected persons attending HIV-specialty clinics living in non-urban Alabama and Mississippi to ascertain the likely geographic origins of their infections, determine their post-HIV diagnosis mobility, and identify predictors of this mobility. Most subjects (81%) were living in these two states when diagnosed and have not moved since learning of their HIV status (70%). Of those who moved their primary residence post-HIV diagnosis (25% of the entire study population), the majority in-migrated to Alabama or Mississippi from elsewhere. Persons who had moved post-HIV diagnosis were more likely to be male, an injection drug user, an urban resident at HIV diagnosis, have an AIDS-defining condition, and have moved prior to HIV diagnosis. We conclude that most HIV transmission in non-urban Alabama and Mississippi is acquired locally. These results underline the need to expand HIV prevention programs in the Deep South.