The purpose of this study was to examine the independent and interactive effects of HIV-1 serostatus and cocaine on neuropsychological (NP) performance in a sample of 237 gay and bisexual urban-dwelling African American men. Consistent with current evidence, it was expected that the greatest neuropsychological performance deficits would be evident (1) in the symptomatic seropositives (SSPs), especially in domains affected by HIV (i.e., memory and psychomotor speed), and on tests that are sensitive to subtle slowing; (2) in those who are recent and frequent cocaine abusers; and (3) in those who are both HIV seropositive and cocaine abusers. Multivariate analyses controlling for age and alcohol use confirmed expectations, with symptomatic seropositives (SSPs) evidencing significantly poorer psychomotor speed than the seronegatives (SNs), and slower reaction time and poorer nonverbal memory than the asymptomatic seropositives (ASPs). Moderate to heavy recent cocaine use was associated with slower psychomotor speed. However, contrary to expectations, no interaction of serostatus and cocaine was noted for any NP domain, and the expected serostatus and cocaine effects on verbal memory and frontal systems were not obtained. Level of alcohol consumption exacerbated the detrimental effects of HIV-1 on a computerized reaction time test which is especially sensitive to subtle slowing. This study provides one of the first descriptions of the neuropsychological effects of HIV-AIDS in a non-injection drug-using community sample of gay and bisexual African American men.