Epidemiologic studies suggest that ozone (O(3)) and airborne particulate matter (PM) can interact causing acute respiratory inflammation and other respiratory diseases. Recent studies investigated the hypothesis that the effects of air pollution caused by O(3) and PM are larger than the effect of these two pollutants individually. We investigated the hypothesis that ozone and traffic-related PM (PM(10) and PM(2.5), diesel and gasoline exhaust particles) interact synergistically to produce increasing amounts of highly reactive hydroxyl radicals (HO) in a heterogeneous aqueous mixture at physiological pH. Electron paramagnetic resonance (EPR) and spin trapping were used for the measurements. Results showed that HO radicals are generated by the catalytic action of PM surface area with ozone and that EPR peak intensities are two to three times higher compared to PM samples without ozone. Incubation of the nucleoside 2'-deoxyguanosine (dG) in aqueous mixtures of ozone and PM at pH 7.4 resulted in the hydroxylation at C(8) position of dG. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed a 2-2.5-fold increase over control (PM without O(3)). These results suggest that PM and O(3) act synergistically generating a sustained production of reactive HO radicals. Partitioning of O(3) into the particle phase depends on the concentration, hygroscopicity and particle size.