The reactions of the water-soluble complexes [NiCR](2+) (where CR = 2,12-dimethyl-3,7,11,17-tetraazabicyclo[11.3.1]heptadeca-1(17),2,11,13,15-pentaene) and [NiKGH-CONH2](+) (where KGH-CONH2 = lysylglycylhistidinecarboxamide) with sulfite/O-2 and peroxymonosulfate have been investigated using spectrophotometric and rapid-scan techniques. In most cases, the spectral changes suggest the formation of an intermediate Ni(III) species, followed by decomposition reactions which involve a back-reaction to Ni(II). Only in the case of the [NiCR](2+)-S(IV)-O-2 system is the formed Ni(III) species stable in solution. When sulfite and oxygen an used to oxidize Ni(II) to Ni(III), the reaction is oxygen dependent and an induction period could be observed, whereas the use of the strong oxidizing agent peroxymonosulfate resulted in no induction period and no oxygen dependence-In addition, the oxidation of Ni(II) to Ni(III) was faster if peroxymonosulfate was used instead of sulfite/O-2. The [NiKGH-CONH2](+) complex reacts much faster with sulfite/O-2 and peroxymonosulfate than the [NiCR](2+) does. Rate constants for the oxidation process and possible reaction mechanisms, based on available literature data, that can account for the observed kinetic observations in a qualitative way are presented, and the results are correlated with previously obtained data on DNA modification using these systems.