Prompt and effective treatment is a fundamental component of the global strategy for malaria control. However, control efforts are hampered by drug resistance. The objective of our work was to determine the relationship between the mutations of Plasmodium falciparum and resistance to Chloroquine (CQ) and Sulfadoxine-Pyrimethamine (SP); more specifically to understand how these mutations relate to each other and their role in predicting resistance. The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in P. falciparum was explored in samples from patients with uncomplicated malaria tested in vitro and in vivo with CQ. The 2 mutations were strongly related. We computed, according to the prevalence of the Pfcrt T76 mutation, the genotype failure index (GFI) in 4 sites in Burkina Faso for 2 different years (1998 and 2001) and related it to the prevalence of CQ resistance estimated by in vivo test in 1998-1999 and 2000-2001. In 3 sites, the GFI varied between 1.7 and 3, a result confirming the constant relationship between the Pfcrt T76 and CQ resistance.