We conducted a double-blind, placebo-controlled study to evaluate the efficacy and tolerability of transdermal scopolamine in the prevention of motion sickness (MS) aboard a frigate during 7 days of continuously moderate or heavy seas. Forty-nine healthy sailors with a previous history of MS were randomly assigned to receive a transdermal therapeutic system of scopolamine (TTS-S) or transdermal placebo (TD-P). Patches were placed behind the ears at least 4 hours before departure and were removed 72 hours later. Subjects were observed on days 1 to 4 and 6. In the TTS-S group, both subjective feeling of MS and the incidence of nausea were reduced during the first 2 days. Because of adaptation, differences in signs and symptoms of MS between subjects receiving TTS-S and TD-P disappeared after the second day. During the first 3 days, vomiting occurred less often in the TTS-S group. On day 6, 3 days after removal of the patch, vomiting occurred in 23% of the TTS-S group, probably due to delay in adaptation, but none of the subjects in the TD-P group vomited. Concentration was not adversely influenced, since the ability to work increased in the TTS-S group. During prolonged continuous exposure to heavy and moderate seas, 2.5 cm2 TTS-S discs proved to be efficacious in preventing MS, with xerostomia as a tolerable side effect and no significant ocular side effects.