The efficacy of transdermal therapeutic system of scopolamine (TTS-S) in the prevention of sea sickness and the extent of its side effects were evaluated in 130 male healthy sailors (volunteers) in a placebo-controlled, double-blind, randomized study. TTS-S or transdermal placebo (TD-P) were placed behind ears 12 hours before departure and removed 72 hours later. It was found that the severity of motion sickness in the TTS-S group was significantly milder than that in the TD-P group. The TTS-S had no statistically significant side effects when compared with the TD-P. The levels of histamine in the blood of 10 subjects, with or without TTS-S, were measured following experimental motion sickness induced by Coriolis test, and the induced optokinetic rotational nystagmus was recorded. The results demonstrated that the level of blood histamine increased after motion sickness, it was higher in the subjects with TTS-S, and there was no significant difference for the optokinetic rotational nystagmus between groups. These findings suggested that histamine contribute to the development of motion sickness and scopolamine may play anti-motion sickness action by blocking the H1-receptor.