The effect of alpha-ketoglutarate (alpha-KG) on circadian patterns of lipid peroxides and antioxidants in N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in rats has been studied. The circadian rhythm characteristics (acrophase, amplitude, and mesor) of thiobarbituric acid-reactive substances (TBARS), antioxidants, superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione were markedly altered in NDEA-treated rats. The delays in acrophase observed in NDEA-treated rats were brought back to near normal range by the administration of alpha-KG. An increase in mesor values of TBARS and a decrease in mesor values of antioxidants in NDEA-administered rats were reversed by alpha-KG administration. It can be concluded that alpha-KG exerts its chemopreventive effect by restoring antioxidants and their circadian rhythms.