This mini-review summarizes results of studies on the oxidation of proteins and low-density lipoprotein (LDL) by various mixed-function oxidation (MFO) systems. Oxidation of LDL by the O-2/FeCl3/H2O2/ascorbate MFO system is dependent on all four components and is much greater when reactions are carried out in the presence of a physiological bicarbonate/CO2 buffer system as compared to phosphate buffer. However, FeCl3 in this system could be replaced by hemin or the heme-containing protein, hemoglobin, or cytochrome c. Oxidation of LDL by the O-2/cytochrome P450 cytochrome c reductase/NADPH/FeCl3 MFO system is only slightly higher (25%) in the bicarbonate/CO2 buffer as compared to phosphate buffer, but is dependent on all components except FeCl3. Omission of FeCl3 led to a 60% loss of activity. These results suggest that peroxymonobicarbonate and/or free radical derivatives of bicarbonate ion and/or CO2 might contribute to LDL oxidation by these MFO systems. Published by Elsevier Inc.