Dietary reference intakes (DRIs) for vitamin C for healthy U.S. populations are currently being formulated by the Panel on Dietary Antioxidants and Related Compounds of the Food and Nutrition Board of the Institute of Medicine. A major task of the Panel is to analyze the evidence of adverse effects of high-dose vitamin C intakes to derive, if appropriate, a Tolerable Upper Intake Level (UL) for vitamin C. The present report details current and past research examining potential adverse effects of supplemental vitamin C. The available data indicate that very high intakes of vitamin C (2-4 g/day) are well tolerated biologically in healthy mammalian systems. Currently, strong scientific evidence to define and defend a UL for vitamin C is not available.