INTRODUCTION: Motion sickness adversely affects military air and sea operations. Medications help prevent motion sickness but are frequently associated with side effects. Better medications or combinations of medications are needed. Dextroamphetamine has documented anti-motion sickness effects but also has a potential for abuse. Modafinil is a relatively new central nervous system stimulant that has none of the drawbacks of dextroamphetamine, but has not been evaluated for the treatment of motion sickness. METHODS: This double-blind, placebo-controlled study evaluated the anti-motion sickness efficacy of modafinil, alone or in combination with oral scopolamine. Moderate nausea was induced via a Coriolis cross-coupling stimulus. There were 60 participants who were assigned randomly to 1 of 3 conditions: 1) 2 placebo pills (DP); 2) modafinil plus placebo (MP); or 3) modafinil plus oral scopolamine (MS). The primary measure of drug efficacy was the number of head tilts tolerated upon reaching moderate nausea for 1 min without abatement. RESULTS: The combination of modafinil and scopolamine (MS) allowed subjects to tolerate significantly more head tilts than placebo, but modafinil alone (MP) failed to differ significantly from placebo (DP). No significant cognitive performance decrements were observed among the three experimental conditions. CONCLUSION: Modafinil was not found to be more effective than placebo. Further testing is recommended to determine whether the potentially promising combination of modafinil and scopolamine provides better efficacy or fewer side effects than scopolamine administered alone.