HIV-seropositive (HIV+) drug users show impaired performance on measures of integrity of prefrontal-subcortical systems. The Iowa Gambling Task (GT) is mediated primarily through ventromedial-prefrontal systems, and poor performance on this measure ("cognitive impulsivity") is common among substance dependent individuals (SDIs) as well as patients with disease involving prefrontal-subcortical systems (e.g., Huntington disease). We hypothesized that HIV+ SDIs might be more vulnerable to cognitive impulsivity when compared with HIV-seronegative (HIV-) SDIs because recent studies report evidence of additive effects of HIV serostatus and drug dependence on cognition. Further, working memory is considered a key component of GT performance and is reliably impaired among HIV+ SDIs compared to controls. We administered the GT to 46 HIV+ and 47 well-matched HIV- males with a past or current history of substance dependence. In addition, we evaluated correlations between subjects' scores on the GT and on a delayed nonmatch to sample (DNMS) task in order to test if working memory deficits accounted for cognitive impulsivity among the HIV+ subjects. The HIV+ subjects performed significantly more poorly on the GT compared to the HIV- group but this effect could not be explained by working memory deficits. Implications of these findings for future basic and applied studies of HIV and substance dependence are discussed.