This report explores the hypothesis that the presence of HIV infection in rural south west Uganda is associated with socioeconomic status and gender. As part of an ethnographic, medical, and serological survey in 15 villages in Masaka district, population 9,950 persons, data were collected on a series of possible socioeconomic indicators. Serological specimens were collected from all consenting individuals for the determination of HIV serostatus. In five selected study villages, there was a good correlation between wealth rankings made by selected local residents and four socioeconomic indices, namely, type of dwelling, available land size, ownership of cattle, and an index of household items. These indices were applied to the full data set to rank the households in all villages. The resulting ranking was matched against HIV-1 status of household heads and, subsequently, their first-degree relatives. Analyzing the data from the 15 villages combined, there was evidence from all four indicators that both male and female heads of the poorest households were most likely to be HIV positive. The increased risk of HIV infection of the poor may be due in part to the income-generating strategies they adopt to survive.