To review the natural history of HIV infection in older women, a retrospective review of women enrolled in the HIV Outpatient Program based at the Medical Center of Louisiana in New Orleans was performed. Eighty-four of the women were at least 40 years of age. Older women were more likely to be diagnosed with selected psychosocial illnesses (e.g., injection drug use, alcohol abuse, anxiety, depression, psychosis, dementia) compared with women <40 years of age. There was no association with age and other opportunistic processes or HIV-related symptoms, but cervical dysplasia and chlamydia cervicitis were less common in older women. In a multivariate proportional hazards model, characteristics predictive for death among older women included a CD4 cell count <200 cells/mm3 (relative risk [RR], 2.86; 95% confidence interval [CI], 1.18, 6.86; p < .02), a diagnosis of an opportunistic process (RR, 3.25; 95% CI, 1.24, 8.55; p < .02), antiretroviral combination therapy (RR, 0.36; 95% CI, 0.12, 1.13: p < .08), and hormone replacement therapy (HRT) (RR, 0.28; 95% CI, 0.07, 1.10; p < .06). HRT should be considered in the management of postmenopausal HIV-infected women for its known documented benefits shown in populations of persons not infected with HIV. Prospective studies to better evaluate risks and benefits of HRT in HIV-infected women are warranted.