Nonenzymic oxidation of caffeic acid (CA) was studied at pH's 4.0 through 8.0, at various concentrations (1 to 10 mM) and at 5, 20 and 35°C. The products of CA oxidation were investigated by high-performance liquid chromatography (HPLC) with diode array detection. The proportion of different oxidation products formed from the CA was affected by the conditions, but the major products were formed in each case and gave a constant chromatographic profile under a given set of conditions. The rate of the reaction was increased greatly by increasing pH and by temperature. The Arrhenius activation energy was 49.0 ± 6.4 kJ mol-1 at pH 8.0 for CA oxidation. Brown (420 nm) generation correlated well (P 0.001) with CA consumption at all pH's and temperatures. Oxidation products were purified by preparative reversed-phase HPLC and their structures deduced from 1H and 13C NMR, UV-visible spectrophotometry and mass spectrometry. These oxidation products were dimers and trimers of CA and were formed by reactions involving the side chain of at least one of the CA units. Their structures have dioxan, furan, or cyclohexene bridges between the caffeic units. Phenolate ions and semiquinones are involved in the formation of these products. Initial oxygen uptake by ortho-dihydroxybenzenes is slowed by adding thiols like cysteine (Cys) or glutathione (GSH) and increased the total amount of oxygen consumed. Combined with CA, phenols like phloroglucinol and catechin increased total oxygen uptake even further compared to the components individually, and still more with the addition of thiols. Reversed-phase HPLC was used to study the reactions of CA with Cys during chemical autoxidation. The formation and disappearance of 2-S-cysteinyl caffeic acid (2-CCA), 5-S-cysteinyl caffeic acid (5-CCA) and 2,5-di-S-cysteinyl-caffeic acid (DCCA) were investigated. CA disappearance during oxidation correlated with brown (420 nm absorbance) formed. Thiol additions had protective effects on CA consumption which increased at higher thiol concentrations and lower pH's by addition and by reduction. A golden yellow color measured by 420 nm absorbance is produced at pH's 9 and higher which only becomes an objectionable brown once Cys is depleted. Yellow color intensified as more CA is oxidized. When Cys is depleted CA and its thioethers are rapidly oxidized with formation of brown rather than yellow color. Concentrations of either GSH or ascorbic acid equimolar with CA had large protective effects against browning and CA disappearance at pH 7.0 (where Cys had little effect) by reducing its quinone back to CA.