In areas of intense malaria parasite transmission, preliminary studies of the rate of reinfection after curative therapy suggest that small sample size studies of vaccine efficacy are feasible. However, the effect of transmission rate, which may vary considerably between transmission seasons, on reinfection rate has not been assessed in areas of mesoendemicity with seasonal transmission. To address this question, the Plasmodium falciparum reinfection rate after curative therapy was measured in Sotuba, a Malian village with historically low transmission rates, as estimated by the entomological inoculation rate (EIR). The reinfection rate after curative Fansidar (sulfadoxine-pyrimethamine) treatment was 80.7% (88/109). The EIR during the 13-week study period (seasonal transmission) varied between 1 and 4.5 infected bites/person/month. The finding that reinfection rates were high despite low EIRs suggests that a low EIR may be sufficient to support small sample size vaccine efficacy trials in mesoendemic areas.