Sir—The multicenter randomized trial reported by Overbosch and colleagues [1] is important for 2 reasons. First, the study shows that when taken as malaria prophylaxis, mefloquine is not well tolerated by many travelers. Of the study participants randomized to receive mefloquine, 67.1% reported 1 adverse event, and, in 6% of mefloquine users, these events were severe (defined as requiring medical advice). The most common category of unwanted effects in the mefloquine treatment arm were neuropsychiatric adverse effects, which were reported by one-third of all mefloquine users [1]. This disturbing finding contradicts the advice in the most recent guidelines on malaria prevention for US travelers issued by the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia); the guidelines state that “mefloquine is the drug of choice for chemoprophylaxis for most travelers [and] is well tolerated at prophylactic dosages” ([2], p. 1767). This assurance, which is plainly incorrect, was based on findings from uncontrolled studies of tourists and Peace Corps volunteers and from mefloquine trials that involved young, healthy soldiers. The CDC guidelines urgently need to be revised now that a randomized trial involving heterogeneous, nonimmune travelers has provided good evidence that mefloquine prophylaxis has the potential to cause harm.