Due to the spread of chloroquine-resistant strains of Plasmodium falciparum in French speaking parts of Africa, we have found it necessary to prescribe mefloquine for antimalaria prophylaxis to travelers to this area. Weekly doses of 125 or 250 mg have been recommended for short journeys. In spite of this regimen, 16 documented cases of falciparum malaria in travelers have been recorded in the Bordeaux hospital center since October, 1988. Fifteen of these patients were tourists returning from West African countries, and one was an Ivorian student who had been on vacation to his home country. Nine of these patients were evaluated and found to have high plasma mefloquine levels. This report strongly supports the existence of mefloquine-resistant falciparum malaria in West Africa, especially in Sierra Leone, Burkina Faso, and Cote d'Ivoire.