The physiology of nausea, a uniquely human symptom, is poorly understood. The purpose of this study was to measure the temporal sequences of neurohormonal responses and gastric myoelectrical activity in healthy subjects during the rotation of an optokinetic drum that produced nausea and other symptoms of motion sickness. Plasma catecholamines, vasopressin, and cortisol were measured at baseline, during minutes 1-5, 6-10, and 11-15 of drum rotation, and after rotation stopped. Electrogastrograms were recorded throughout the study. Twelve subjects (80%) developed nausea and 4-9 cycles/min of gastric tachyarrhythmias; three subjects had no nausea and no gastric dysrhythmias. Tachyarrhythmias began 3.4 +/- 0.8 min after the onset of drum rotation, and nausea was reported, on average, 3 min later. During minutes 6-10 of drum rotation, vasopressin levels significantly increased in the subjects with nausea compared with subjects without nausea (P < 0.04). In the subjects with nausea, epinephrine and vasopressin increased significantly (P < 0.05) compared with baseline during minutes 6-10 and 11-15 of drum rotation. As nausea resolved during recovery, vasopressin decreased by 74%, whereas epinephrine increased 13%. We conclude that 1) in nauseated subjects, endogenous vasopressinergic and sympathetic circuits are activated before hypothalamic-pituitary-adrenal pathways, 2) plasma vasopressin levels correlate most closely with the temporal onset and resolution of nausea, and 3) peripheral gastric dysrhythmias may have a role in activating central vasopressinergic neurons.