Objectives To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. Design One-year follow-up (1990–1991) in a population-based rural cohort. Setting and participants Annual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters in Rakai District. Subjects provided yearly HIV serological samples, behavioral and health information. Main outcome measure Mortality in HIV-infected and uninfected persons. Results Mortality among HIV-seropositive adults aged ≥15 years of 118.4 per 1000 person-years (PY) was substantially higher than in HIV-seronegative adults [12.4 per 1000 PY; relative risk (RR), 9.5; 95% confidence interval (CD, 6.0–14.9]. Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women (210 compared with 111 per 1000 live births; RR, 1.9; 95% Cl, 1.0–3.5). Adult HIV-related mortality was associated with HIV prevalence and, in this cohort, with higher education, non-agricultural occupation and residence in roadside trading centers. We estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined, district HIV attributable mortality is 28%. Conclusion HIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However, the overall crude birth rate in the district (45.7 per 1000 population) remains higher than the crude death rate (28.1 per 1000 population), resulting in continued rapid population growth.