The response of plasma arginine vasopressin (AVP) to nicotine administered by chewing gum (Nicorette, 2 mg) was examined in nine healthy volunteers. Heart rate, mean arterial pressure, serum osmolality, plasma AVP level, and plasma nicotine level were measured at baseline (control) and at 30, 45, and 60 minutes after initial administration of the gum. There were small increases in heart rate (72 ± 6.3 to 82 ± 5.1 beats/min, p < 0.05) and mean arterial pressure (88 ± 8.2 to 93 ± 10 mm Hg, p = NS), while the plasma nicotine level increased to a maximum of 16 ± 2.0 ng/ml (p < 0.001). No changes were seen in either osmolality (283 ± 3.4 mOsm/kg) or AVP level (4.3 ± 2.0 pg/ml) in eight of the nine subjects who remained asymptomatic. In one subject whose hemodynamic and plasma nicotine responses were similar to the others but who became nauseated, the plasma AVP level increased from 4.2 to 26 pg/ml. These data suggest that nicotine at the plasma concentrations achieved in this study is not associated with stimulation of plasma AVP secretion in normal man. Other factors in association with nicotine use, in this case nausea, may be required for AVP stimulation to occur.