Oxidative stress induced by nicotine was investigated in the esophageal mucosa of rats. The homogenized mucosa was incubated for 30 min with 50, 100, 200, 400, and 800 ng/mg protein/ml nicotine or with 200 ng/mg protein/ml nicotine for 15, 30, 45, and 60 min. Esophageal mucosa was also incubated for 30 min with 200 ng/mg protein/ml nicotine with or without the scavengers superoxide dismutase (SOD), catalase, SOD+catalase, inactivated SOD, inactivated catalase, or albumin. Incubation with 0.9% NaCl served as control. There was a strong correlation between chemiluminescence and the nicotine dose (r = 0.75) or the nicotine incubation time (r = 0.77). Thirty-minute incubation of the esophageal mucosa with 200 ng/mg protein/ml nicotine increased chemiluminescence 5.5-fold and lipid peroxidation 3.3-fold. This response was dampened by SOD or catalase and abolished by SOD+catalase. Inactivated enzymes or albumin had no scavenging effect. These results demonstrate that nicotine causes oxidative stress to the esophageal mucosa.