The antioxidative effects of dietary a-tocopherol (TOC) and riboflavin-tetrabutyrate (RTB) against tissue lipoperoxidation caused by the long-term administration of methyl linoleate hydroperoxide (HPO) to rats were investigated by measuring the spontaneous chemiluminescence (CL) intensities and thiobarbituric acid (TBA) reactants of the liver, lung and heart. TOC supplementation resulted in the effective decrease of CL intensities and TBA reactants in the three organs, while RTB supplementation led to the definitive decay of both indices of the lung and a significant decrease in the CL intensity of the heart, as compared with thoseof rats dosed with HPO and not given any supplemental antioxidant. Although the activities of glutathione peroxidase and glutathione reductase in the three organs obtained from rats dosed with HPO for 29 days were clearly lower than those of thecontrol rats, both enzyme activities in rats dosed with antioxidants other than HPO were generally maintained at levels almost equal to those of the control rats. Glutathione peroxidase ofthe liver and heart and glutathione reductase of the liver were shown to be further activated bythe simultaneous supplementation of TOC and RTB. The results indicated that both TOC and RTB effectively act as antioxidants in rats dosed with HPO over a long-term. One of the antioxidative actions of both agents is ascribed to protection of the glutathione peroxidase system in organs undergoing lipoperoxidation caused bythe long-term treatment of dietary hydroperoxides.