A descriptive retrospective study on the AIDS and HIV patients of rural eastern North Carolina was performed. Our data show what appears to be a ‘second wave’ of HIV-related disease (HRD) in this area. Although most of our AIDS and HIV patients migrated from urban areas such as New York State, our patient population is now largely being replaced by locally infected or ‘home-grown’ patients. The epidemiological characteristics of rural HRD are significantly different to those of urban HRD: rural patients are more likely to be female, heterosexual, non-white, and younger. These epidemiological differences, along with limited medical and social services in a poor economic base, will make treating HRD a more difficult problem in rural areas than in traditional urban centers.