Crosslinking of guanine with tyrosine and glutathione is studied by on-line electrochemistry electrospray ionization mass spectrometry (EC ESI MS) in the positive ion mode with a high resolution FT ICR mass spectrometer without the use of an external oxidizer in the sample. Dimeric adducts of guanine with tyrosine (m/z 331) and (m/z 333) and a dimer of guanine with glutathione (m/z 459) are detected in the mass spectra of guanine-tyrosine and guanine-glutathione mixtures in addition to dimers of guanine (m/z 303) and tyrosine (m/z 361) and (m/z 363) and glutathione dimers (m/z 613) and (m/z 615). Guanine tetramers (m/z 627) and tetramers of guanine with 1 or 2 tyrosines, but not with three tyrosines, were also identified in the mass spectra of guanine-tyrosine mixtures. Formation of radicals and other oxidation products during positive ion mode ESI can drive the formation of covalent dimer adducts of guanine with tyrosine and glutathione. When low EC cell voltage is applied in on-line EC ESI MS, changes in ion intensities reflect changes in the oxidation conditions and are more apparent for 2e, 2H + than for the 1e, 1H + oxidation processes. Efficient oxidation during ESI is indicated for analytes with low redox potentials.