There is substantial evidence implicating excitotoxicity and oxidative damage in the pathogenesis of Huntington's disease (HD). We therefore examined whether the antioxidants 2-sulpho-tert-phenyibutyinitrone (S-PBN) and α-lipoic acid could exert neuroprotective effects in transgenic mouse models of HD. S-PBN showed no effects on either weight loss or survival in the R6/2 transgenic HD mice. α-Lipoic acid produced significant increases in survival in both R6/2 and N171-82Q transgenic mouse models of HD. These findings suggest that α-lipoic acid might have beneficial effects in HD patients.