We studied the polymorphism of msp-1, which encodes a major surface protein on the merozoite, isolated from blood samples from western Thailand in 1999. Our study area was a low-transmission area for malaria, where mefloquine has been used as an antimalarial drug since 1994. Forty-nine patients were confirmed to have contracted falciparum malaria twice within 24 weeks. The number of detected haplotypes in 49 patients was 89 at the first diagnosis and 68 at the second diagnosis. The mean number of haplotypes per patient significantly decreased from 1.82 to 1.39 but the frequency distributions of msp-1 haplotypes did not change significantly with the use of mefloquine. Our study strongly suggests that the antigenic diversity of Plasmodium falciparum is retained during mefloquine therapy in low-transmission areas.