Plasmodium malariae is regarded as usually being susceptible to all anti-malarials whether applied for prophylaxis or treatment. We report on three cases of P. malariae infection which occurred 12-14 weeks after anti-malarial chemoprophylaxis or treatment with mefloquine or atovaquone/proguanil. The most likely explanation for the failure of mefloquine and atovaquone/proguanil to prevent quartan malaria occurring some months later is the insufficient effect on the particularly long-lasting pre-erythrocytic development stages of P. malariae.