Background: Mefloquine (MQ) is an important antimalarial drug. Dizziness and other adverse neuropsychiatric reactions have however restricted its use. Method: Ten healthy adult volunteers were given MQ (Lariam) 250 mg once weekly for 16 weeks. Measurement of postural sway (posturography), nystagmus recording, determinations of hearing thresholds (Bekesy audiometry), and determinations of drug concentrations were done before, after 4, 32, and 109 days of weekly MQ intake and 3 months after the last dose. Results: All volunteers were able to continue their professional work and normal daily activities. Several mild symptoms were reported. In at least one of the volunteers, these symptoms were probably caused by the MQ intake. Hearing thresholds remained normal. No significant changes were noted in the nystagmus tests. The recorded values of sway index were within the normal range (99% confidence interval) in all volunteers in all test situations, and no differences were seen at the time of maximal drug concentrations (day 109) compared to before or after the study. There was no correlation between the plasma concentrations of MQ, the two MQ enantiomers (RS and SR), or the main mefloquine metabolite and the sway index. Conclusion: Although no effect was seen on the vestibular system in the present study, further tests in a flight simulator will be needed before MQ can be recommended for pilots. (J Travel Med 2:66-69, 1995)