This study examines the influence of HIV-seropositivity and antiviral medications on cerebral blood flow in cocaine abusers. Forty-five HIV negative (HIV-) cocaine abusers, 36 HIV positive (HIV+) cocaine abusers (CD4; mean 378, +/-229) and 27 control HIV- subjects were studied. Blood flow velocity and pulsatility were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography (TCD). Psychological assessments, which included the psychiatric symptom checklist (SCL-90R), hopelessness (Beck) and well-being (Ellison) questionnaires revealed greater psychiatric distress in HIV+ cocaine abusers than the other groups. HIV- cocaine abusers and HIV+ cocaine abusers not receiving antiviral medications (n=25 of 36) had elevated pulsatility values, indicating increased resistance in the cerebral blood vessels in comparison to control subjects. HIV+ cocaine abusers using antiviral medications (n=11 of 36) had pulsatility values similar to HIV- control subjects. Interestingly, there was no significant relationship between intensity of psychiatric distress reported by HIV+ cocaine abusers and perfusion deficits. Our findings suggest that unmedicated HIV+ cocaine abusers have cerebrovascular deficits, which are similar to HIV- cocaine abusers. In addition, the use of antiviral medications appears to be associated with a reduction of these deficits in HIV+ cocaine abusers. Nevertheless, more studies will be needed before any conclusion can be reached regarding possible beneficial effects of these agents on the cerebral vasculature.