Astroglial cells represent a target for HIV infection in the central nervous system. In astrocytes, HIV infection is poorly productive, being characterized by a persistent state of viral latency. However, activation of the nuclear factor NF-kappa B and its binding to HIV long terminal repeat (LTR) can induce HIV replication. Moreover, nitric oxide (NO) can affect NF-kappa B activation in glial cells. Therefore, we hypothesize that NO may reduce HIV replication in human astroglial cells by inhibiting HIV-1 LTR transcriptional activity. In this respect, we show that NO donors reduce viral replication in HIV-l-infected human astrocytoma T67 cells, taken as an astroglial model, Furthermore, using transfected T67 cells, we demonstrate that NO donors inhibit HIV-1 LTR transcriptional activity. These results suggest that the use of NO-releasing drugs may represent a potential, novel approach in inhibiting HIV replication in the central nervous system. (C) 1999 Academic Press.