Reactions of the substituted methyl radicals CH2OCH3,CH2NH2,CH2I, and CH2CN with O-2 have been studied by a combination of pulsed laser photolysis and photoionization mass spectrometry. The reactivity is greatly enhanced by substituting one of the hydrogen atoms of a methyl radical with the electron-donating substituents, -OCH3 and -NH2. The rate constants obtained at 298 +/- 5 K were (6.5 +/- 0.7) x 10(-12) and (3.5 +/- 0.4) x 10(-11) in units of cm(3) molecule(-1) s(-1) for CH2OCH3 and CH2NH2, respectively, and no pressure dependence was observed between 0.6 and 6 Torr (80-800 Pa) of N-2 as a bath gas. The reactivity is reduced for CH2I and CH2CN, which have the electron-withdrawing substituents -I and -CN. The rate for the reaction of CH2I with O-2 was independent on the total pressure between 2 and 15 Torr (270-2000 Pa) of N-2, and the rate constant was determined to be (1.6 +/- 0.2) x 10(-12) cm(3) molecule(-1) s(-1). The rate constants of CH2CN with O-2 depended on the total pressure, and were (6.8-11.0) x 10(-15) cm(3) molecule(-1) s(-1) for total pressures 2-6 Torr (270-800 Pa) of N-2 + O-2. The reactivity of substituted methyl radicals is discussed by the correlation with ionization potentials and electronegativities of radicals.