The intake of phenolic acids and related polyphenolic compounds has been inversely associated with the risk of heart disease, but limited information is available about their bioavailability or mechanisms of action. Polyphenolics, principally avenanthramides, and simple phenolic acids in oat bran phenol-rich powder were dissolved in HCl:H2O:methanol (1:19:80) and characterized by HPLC with electrochemical detection. The bioavailability of these oat phenolics was examined in BioF1B hamsters. Hamsters were gavaged with saline containing 0.25 g oat bran phenol-rich powder (40 μmol phenolics), and blood was collected between 20 and 120 min. Peak plasma concentrations of avenanthramides A and B, p-coumaric, p-hydroxybenzoic, vanillic, ferulic, sinapic, and syringic acids appeared at 40 min. Although absorbed oat phenolics did not enhance ex vivo resistance of LDL to Cu2+-induced oxidation, in vitro addition of ascorbic acid synergistically extended the lag time of the 60-min sample from 137 to 216 min (P ≤ 0.05), unmasking the bioactivity of the oat phenolics from the oral dose. The antioxidant capability of oat phenolics to protect human LDL against oxidation induced by 10 μmol/L Cu2+ was also determined in vitro. Oat phenolics from 0.52 to 1.95 μmol/L increased the lag time to LDL oxidation in a dose-dependent manner (P ≤ 0.0001). Combining the oat phenolics with 5 μmol/L ascorbic acid extended the lag time in a synergistic fashion (P ≤ 0.005). Thus, oat phenolics, including avenanthramides, are bioavailable in hamsters and interact synergistically with vitamin C to protect LDL during oxidation. J. Nutr. 134: 1459-1466, 2004.