Objective: To examine the involvement of cognitive function in HIV‐seropositive drug users (DU) in a pre‐AIDS state. Design: Fifty‐six HIV‐positive DU were prospectively evaluated. They belonged to groups II, III and IV (subgroups A, C2 and E) of the 1987 Centers for Disease Control and Prevention classification, with anamnesis negative for neurological pathology. HIV‐negative DU (n = 19) and non‐DU (n = 27) were used as controls. Infection with HIV and use of toxic drugs were considered variables of influence on cognitive function. Method: Subjects underwent neuropsychological evaluation by tests designed to explore cortical and subcortical function. Results: HIV‐positive DU showed worse performance scores at the psychometric tests than HIV‐negative non‐DU, but there was no difference when compared with HIV‐negative DU. Ex‐DU showed better performance than active DU. No difference with regard to degree of disease evolution was observed among HIV‐positive individuals (i.e., groups II and III versus group IV). Conclusions: There was no evidence of cognitive deficits in HIV‐positive individuals in non‐AIDS phases to indicate early involvement by HIV at the cerebral level. Progression of the disease, prior to the AIDS phase, did not determine a worsening of intellectual performance. Instead, cognitive function was affected by the chronic and current use of toxic substances. In HIV‐positive DU, a decline in cognitive function was found to be attributable to the chronic use of toxic substances rather than HIV infection.