Outcomes for middle-aged and older individuals with HIV infection are poor, and are likely to be mediated by age-related differences in risks and resources (access to care, relationship with the provider, comorbid conditions, health habits, and changes brought about by aging). The goal of the Veterans Aging Cohort Three-Site Study (VACS 3) is to study the influence of age and mediating factors on outcomes with HIV in order to identify mutable mediators of poorer outcomes. VACS 3 is an observational, longitudinal study. Data sources include patient and provider surveys and electronic medical data collected at baseline and 12-month follow-up from the Infections Disease Clinics at three Veterans Affairs Medical Centers (Cleveland, OH, Houston, TX, and Manhattan, NY). Trained Survey Coordinators at each site determined which patients are HIV infected, obtained consent, and asked the patient to complete a questionnaire. The primary provider also completed a questionnaire. Twelve-month follow-up will be completed July 2001. Of all veterans with HIV seen in these clinics 85% (881) have consented and enrolled. Of the 881 corresponding provider surveys, 92% were completed. Mean age is 49; 55% are African-American; 38% of the sample were men who have sex with men; and less than 2% are women. Almost a third (32%) have been without a permanent address. Complimentary or alternative therapies are common as are the use of cigarettes, alcohol, and illicit drugs. The majority (87%) of the patients are taking multiple antiretroviral medications. The median CD4 count is 331 mm(3), and the median viral load was 714 copies/ml. There is substantial variation by site. Veterans with HIV infection have characteristics that will likely become more prevalent among HIV-infected persons in the United States: they are older, commonly suffer comorbid disease, and are members of minority populations. VACS 3 may help inform the design of future clinical interventions to improve outcomes for people aging with HIV.