We evaluated neurocognitive function in 149 HIV-seropositive and 82 seronegative women enrolled in the Women's Interagency HIV Study (WIHS), a large multi-center study of disease progression in women living with HIV/AIDS. We evaluated the prevalence of abnormal neuropsychological (NP) test findings in HIV-seropositive and seronegative women and factors associated with increased risk of abnormal NP test performance. Risk of NP impairment was no higher for HIV positive women receiving antiretroviral therapy at testing than for HIV-negative women (OR = 1.00). However, the risk of abnormal NP performance increased significantly for seropositive women not receiving antiretroviral therapy (OR = 2.43). Further, treatment status was a significant predictor of NP impairment in a multivariate analysis that included viral load (OR = 1.48) and CD4 count (OR = 1.08) which were not significant. The multivariate analyses controlled for substance use, age, education, head injury, ethnicity, estimated IQ, and psychological distress. This study emphasizes the critical association of antiretroviral therapy with the risk of neurocognitive impairment in women living with HIV/AIDS. (JINS, 2002, 8, 781–793.)