HIV infection is associated with a marked vulnerability of the dopaminergic system. We found recently that dopaminergic substances increase brain pathology in the simian model of HIV infection. In the current study we used the chronically HIV-infected T-lymphoblasts ACH-2 to elucidate the effects of dopamine (DA) on HIV infection. Cells were exposed to various concentrations of DA for 24 hours. Flow cytometry measurements demonstrated that DA induced a concentration-dependent HIV activation. To study the mechanism of action of DA, cells were treated besides DA with glutathione, one of the main components of cellular defense mechanisms against oxidative stress as well as its indirect precursor N-acetylcysteine. Treatment with these antioxidants attenuated DA-induced-HIV activation indicating that changes in cellular redox states might have been the causative factor for the observed effect. Our data suggest that HIV activation is tightly linked to intracellular oxidant/antioxidant levels and that excessive DA exposure may modulate cellular vulnerability to HIV.