Chronic inflammation is known to be associated with enhanced production of both nitric oxide (NO) and reactive oxygen species such as superoxide (O₂^-) and hydrogen peroxide (H₂O₂). Patients with long-standing ulcerative colitis are also known to be at increased risk of developing colorectal cancer. Although NO and reactive oxygen intermediates alone have been known to damage DNA and to promote a wide array of mutagenic reactions, there is increasing evidence to suggest that the interaction between O₂^- and NO may dictate the type of mutagenic reactions produced at sites where both these free radicals are produced. In the absence of O₂^-, NO will engage in nitrosative chemistry to yield stable N-nitrosamine derivatives of secondary amines and promote nitrosative deamination of DNA bases. As the flux of O₂^- is increased, nitrosation reactions are suppressed and oxidative chemistry is enhanced. Thus, depending upon the fluxes of each radical either nitrosation or oxidation chemistry may predominate. The fundamental understanding between O₂^- and NO may provide new insight in the mechanisms responsible for inflammation-induced mutagenesis.