The literature suggests that nondeclarative, or nonconscious, learning might be impaired among HIV-seropositive (HIV+) individuals compared with HIV-seronegative (HIV-) matched control groups, but these studies have included relatively few women. We administered measures of motor skill and probabilistic learning, tasks with a nondeclarative or procedural learning component that are dependent on integrity of prefrontal-striatal systems, to well-matched groups of 148 men and 65 women with a history of substance dependence that included 45 men and 30 women seropositive for HIV. All participants were abstinent at testing. Compared to HIV- women, HIV+ women performed significantly more poorly on both tasks, but HIV+ men's performance did not differ significantly from that of HIV- men on either task. These different patterns of performance indicate that features of HIV-associated neurocognitive disorder (HAND) cannot always be generalized from men to women. Additional studies are needed to address directly the possibility of sex differences in HAND and the possibility that women might be more vulnerable to the effects of HIV and substance dependence on some neurocognitive functions.