Several hemoglobins and bovine myoglobin are shown to undergo autooxidation reactions promoted by anions. The reduced protein in the presence of oxygen and anion yields the anion complex of the oxidized (Met) species and a second product that is almost certainly superoxide. The second product can be detected by its reduction of cytochrome c3+ at the same rates and in the same amount as the Met species. Anions are increasingly effective as promoters in the same order as their strengths as nucleophiles, e.g. Cl- less than F- less than OCN- less than SCN- less than N3- less than CN-. Rates are directly proportional to anion concentrations. A linear dependence of rate upon [H+] is also observed and can be related to the protonation of a strongly acidic group. Globin from hemoglobin A and hemes with altered 2,4-substituents gave reconstituted hemoglobins that autooxidize at rates that decrease with the electron-withdrawing power of the substituent: acetyl greater than vinyl greater than hydrogen greater than ethyl. Changes in rate with globin structure can be interpreted in terms of steric access to the ligand binding site; the more sterically restricted is the site, the slower is the reaction. The effects of [O2] on the rate vary with the degree of saturation with O2. At high O2 levels (e.g. from saturation to the point where 5% deoxyHbA and 95% oxyHbA are present), a decrease in [O2] results in an increase in the rate of azide-promoted autooxidation. At O2 levels with from 5 to 75% deoxyHbA, the rate remains nearly constant. At still lower levels with oxyHbA less than 25%, the rate decreases as [O2] is lowered. Exposure to CO reduces the rate. The reaction mechanism for anion-induced autooxidation must provide for the stoichiometric formation of a cytochrome c3%-reducing species (presumably, superoxide), the anion acting as a nucleophile in the rate-determining step, the facilitation by protons, the sensitivity of the rate to the electronegativity of heme iron, and the varied effects of [O2] upon the rate. These findings can not be fully accommodated by mechanisms in which the Met species forms either via dissociative loss of superoxide from the oxy species followed by anion binding or via displacement of protonated dioxygen from oxyheme upon nucleophilic attack of the anion at heme iron. A consistent mechanism is the reaction of protonated deoxy species with the anion followed by the reaction of Fe2+-anion complex with O2 to give Fe3+-anion and (formula, see text). Here, the deoxy rather than oxy species is involved in Fe2+ oxidation to Fe3+; O2 can serve as one-electron acceptor but not while serving as an iron-bound ligand. A precise non-iron site for electron transfer from ferrous porphyrin to O2 remains unlocated but a process involving the porphyrin pi-system has analogy in simple heme, flavin, or other organic donor reactions with O2 that yield superoxide...