Cigarette smoke contains two distinct populations of free radicals: one in the tar and one in the gas phase. The tar phase contains relatively stable free radicals, primarily a quinone/hydroquinone (Q/QH2) complex, which can reduce molecular oxygen to produce superoxide, generate hydrogen peroxide, and form hydroxyl radicals. These radicals react with DNA in vitro, possibly through covalent binding. The gas phase of cigarette smoke contains more reactive oxygen- and carbon-centered radicals that are produced by the steady-state oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. These radicals may be responsible for the inactivation of α1-proteinase inhibitor by fresh smoke. Cigarette smoke also oxidizes thiols to disulfides, likely through the action of NO and NO2. The toxicological implications of these radicals include their role in various diseases, including emphysema and cancer. The study discusses the structure and reactivity of these radicals and their potential mechanisms of action in smoking-induced pathology.Cigarette smoke contains two distinct populations of free radicals: one in the tar and one in the gas phase. The tar phase contains relatively stable free radicals, primarily a quinone/hydroquinone (Q/QH2) complex, which can reduce molecular oxygen to produce superoxide, generate hydrogen peroxide, and form hydroxyl radicals. These radicals react with DNA in vitro, possibly through covalent binding. The gas phase of cigarette smoke contains more reactive oxygen- and carbon-centered radicals that are produced by the steady-state oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. These radicals may be responsible for the inactivation of α1-proteinase inhibitor by fresh smoke. Cigarette smoke also oxidizes thiols to disulfides, likely through the action of NO and NO2. The toxicological implications of these radicals include their role in various diseases, including emphysema and cancer. The study discusses the structure and reactivity of these radicals and their potential mechanisms of action in smoking-induced pathology.