The plasma vasopressin response to intravenous nicotine (2 mg) and smoking cigarettes of high (1.2 mg) and low (0.6 mg) nicotine content was studied in healthy young subjects with a history of cigarette smoking. Nicotine administered intravenously had no effect on plasma vasopressin. There was a statistically significant increase in plasma vasopressin after both the low and high content cigarettes, with the high content cigarettes resulting in a significantly greater increase. All three interventions resulted in transient increases in blood pressure and pulse of similar magnitude. These studies indicate that cigarette smoking-induced vasopressin release is not mediated via an action of circulating nicotine, and suggest the presence of an airway-specific mechanism for vasopressin release.