Mefloquine is widely used for prophylaxis in areas with chloroquine-resistant falciparum malaria. As the use of mefloquine has increased, so have the reports on its adverse effects. We sought to evaluate the possible association between serum levels of mefloquine and serious side effects caused by this drug by means of a case-control design study. The study population included 17 patients who presented to emergency rooms or travel clinics with symptoms suggesting serious adverse effects of mefloquine and 28 controls (healthy people, still taking mefloquine after travel). The mean age of the patients and the controls was 31.5 ± 11.6 years and 34 ± 12.2 years, respectively. The percentage of women among the patients was higher than in the control population (76% versus 40%, respectively; P = 0.03). Most of the complaints were related to the central nervous system (13 of 17); 5 patients interrupted their trip and 2 others were hospitalized. No difference in the level of mefloquine in the blood was found between the patients and the control groups. Also, no significant difference was found between mefloquine levels in the blood of men and women. These results suggest that blood levels of mefloquine do not correlate with its severe adverse events. Women tended to be more susceptible than men, despite having similar blood levels of the drug.