It is known that HIV can directly infect the CNS and, as a result of such infection, neuropsychological alterations with cognitive, behavioural and motor manifestations can be developed. In this study we seek to determine whether seropositivity is associated with a poor neuropsychological performance in patients with a history of intravenous drug consumption (n=90). For this purpose we carried out an extensive neuropsychological evaluation and compared their performance with that of two seronegative control groups, one comprised of subjects with no history of drug abuse (n=22), which allowed us to obtain a reference of normal neuropsychological performance, and the other of seronegative subjects with a history of drug abuse (n=48), which allowed us to differentiate whether the performance of the seropositive subjects derives from their history of drug abuse. The results reveal that HIV infection in drug users is associated with deficits in attention, verbal and visual memory, verbal skills, concept formation and reasoning, visual-constructive skills, manual dexterity, and perceptive-motor speed, which cannot be attributed to a history of drug abuse. However, the seronegative drug users also showed some of these alterations, which suggests that seropositivity is not only associated with a decrease in performance in these tasks, but also adds to the alterations seen in seronegative subjects as a consequence of drug abuse.