Oxidation of acetaminophen by human methemoglobin in the presence of H(2)O(2) has been kinetically studied in the present paper. The drug showed a protective effect against the H(2)O(2)-induced irreversible inactivation of the protein, thus indicating the competition among both ligands, H(2)O(2) and acetaminophen for the protein. The stoichiometry of the reaction is variable and depends on relative initial concentrations of H(2)O(2) and the drug owing to their competitive behavior. In addition and unexpectedly, the protein exhibits non Michaelian kinetics against both acetaminophen and H(2)O(2) under steady-state conditions and shows negative co-operativity with Hill coefficients in the 0.3-0.7 range. Therefore, these data were compared to those obtained with myoglobin under similar experimental conditions, and the same results were observed. This led us to propose a mechanism for the peroxidase-like activity of hemoglobin, which accounts for the experimental results obtained herein. The steady-state rate equation for this mechanism has been obtained and is also consistent with the experimental data, thus indicating the goodness of the model proposed herein. The results presented in this work provide new insights into the oxidation mechanism of acetaminophen.