It is proposed that there is biological regulation of the low molecular weight antioxidant (LMWA) status of the body, and that these different antioxidants work in concert and in homeostasis as a system analogous to the regulation of acid-base status (pH). The theoretical design characteristics for such a system include regulation, inducibility, interactivity and balance with the beneficial properties of reactive oxygen species. Testing the hypothesis requires developing suitable methodologies (such as measurement of the redox state) for assessing the total ratio of antioxidant to oxidant activity of both tissues and biological fluids, since it is not clear whether plasma antioxidant status reflects that of the tissues as well. This concept, if accepted, may help explain the contradictions relating to antioxidant therapy and lead to more rational recommendations for dietary intake. It may also help explain the effects of manipulating (increasing/decreasing) specific antioxidants on the overall antioxidant status in health and disease.