We describe the clinical and epidemiological characteristics of human immunodeficiency virus (HIV) infection in patients >55 years of age at the time of diagnosis and make comparisons with younger HIV-infected patients. Patients were selected by stratification according to age (>55 years and <40 years) from a large cohort, and information was obtained by review of charts. Three samples of younger patients were used for general comparison (sample 1), for analysis of progression to acquired immunodeficiency syndrome (AIDS) (sample 2), and for analysis of survival after AIDS (sample 3). We identified 33 patients >55 years of age (30 men and 3 women). The mean age was 60.1 years (range, 55–72). Risk factors included homosexual/bisexual, 22 (67%); blood products, seven (21%); heterosexual, two (6%); and unknown risk, two (6%). HIV encephalopathy tended to be more common in the older group, while Kaposi's sarcoma was more common in younger controls. Older patients more frequently acquired HIV infection via transfusion of blood or blood products (p < 0.005), were more likely to have AIDS at presentation (p < 0.001), progressed to AIDS more rapidly (p< 0.002), and had higher mortality rates (p < 0.001). Transfusion of blood or blood products is an important mode of acquisition of HIV in patients >55 years of age. HIV infection has a more rapid and aggressive course in older patients.