Alpha-lipoic acid, a naturally occuring disulfide-compound that acts as a cellular coenzyme, inhibits replication of HIV-1 in cultured lymphoid T-cells. Alpha-lipoic acid was added 16 hours after infection of the T-cell lines Jurkat, SupT1 and Molt-4 with HTLV IIIB and HIV-1 Wai (a wild type HIV-1 isolate). We observed a dose dependent inhibition of HIV-1-replication in CPE (Cytopathic effect) formation, reverse transcriptase activity and plaque formation on CD4-transformed HeLa-cells. An over 90% reduction of reverse transcriptase activity could be achieved with 70 g alpha-lipoic acid/ml, a complete reduction of plaque-forming units at concentrations of 35 g alpha-lipoic acid/ml. An augmentation of the antiviral activity was seen by combination of zidovudine and low dose of alpha-lipoic acid (7 g/ ml). Trypan blue staining revealed no toxic effects of alpha-lipoic acids on peripheral blood mononuclear cells and T-cell lines even in concentrations of 70 g/ml. Therefore, we propose the inclusion of alpha-lipoic acid into chemotherapy trials in combination with zidovudine.