By combining data from 7 randomised trials which evaluated the efficacy of IPTi against clinical malaria with contemporaneous data on resistance and the frequency of mutations in the dhfr and dhps genes in the study areas, we provide estimates of SP-IPTi protective efficacy at different levels of SP resistance with the aim of providing evidence towards defining the level of resistance at which SP-IPTi no longer provides a clinical protective effect. The gene discussed is DHFR; the disease is malaria.