BACKGROUND Previous research in our laboratory has shown that symptoms of motion sickness are accompanied by the loss of normal 3 cpm activity and the development of tachyarrhythmia in the electrogastrogram (EGG). OBJECTIVE We hypothesized that dimenhydrinate would prevent the development of gastric tachyarrhythmia and reduce symptoms of motion sickness. METHODS Twenty health volunteers were tested in a counter-balanced, within-subject, double-blind design. Subjects were exposed to a rotating optokinetic drum to induce vection after receiving either dimenhydrinate (100 mg) or a placebo on two separate occasions. EGG's were recorded immediately before ingestion of capsules, 1 h after ingestion, and during rotation. Motion sickness symptom reports (SSMS) were obtained prior to and during rotation. RESULTS The average SSMS score was 5.9 points higher after placebo administration than after dimenhydrinate administration (t[19] = 4.87, P < 0.001). Significantly more subjects requested early termination of the rotating drum due to severe symptoms after placebo administration than after dimenhydrinate administration (McNemar's chi 2[1] = 6.00, p < 0.05). Drowsiness reports were significantly higher after dimenhydrinate administration than after placebo administration (t[19] = 2.65, p < 0.05). Analysis of EGG's showed a significant decrease in normal 3 cpm and tachyarrhythmic activity after dimenhydrinate, but no change after placebo (SR[19] = 53, p < 0.02 and SR[19] = 68, p < 0.01 respectively). During drum rotation gastric tachyarrhythmias increased significantly in the placebo condition (SR[18] = -0.61.5, p < 0.01), but not in the dimenhydrinate condition. EGG's were not significantly different between conditions. CONCLUSIONS We conclude that dimenhydrinate reduced motion sickness symptoms at least in part by depressing central nervous system activity and possibly by suppressing abnormal gastric myoelectric activity.