Study objective: To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite–induced methemoglobinemia in human volunteers. Methods: We conducted a randomized, control crossover trial with each subject serving as his own control. Methemoglob-inemia was induced with intravenous sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0. At time 30 minutes, subjects were randomly assigned to treatment with intravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg per hour for 40 minutes) or administration of an equal volume of 5% dextrose in water. Each subject received the alternative treatment after an interval of at least 1 week. Blood methemoglobin concentrations were measured by multiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minutes. Area under the methemoglobin concentration-time curve (AUC) between 30 and 130 minutes was compared between groups using a 2-tailed, paired t test. Results: There were no statistically significant differences in the control and treatment groups with respect to baseline hemoglobin or methemoglobin concentrations, as well as nitrite-induced methemoglobin concentrations at the initiation of treatment (0.85±0.06 g/dL, 0.88±0.04 g/dL; mean±SEM; P =.31). Mean AUC for the control group (77.1±5.7 g·min/dL) was significantly lower than the mean AUC for the treatment group (84.5±4.7 g·min/dL); P = .01). Conclusion: Intravenous NAC failed to enhance methemoglobin reduction in this model. [Tanen DA, LoVecchio F, Curry SC. Failure of intravenous N -acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial. Ann Emerg Med. April 2000;35:369-373.]