future science group Subsequently, when MQR P. falciparum were selected to higher levels of MQ resistance, pfmdr1 was found to be amplified [67] . Halofantrine resistance and QN resistance increased with increasing pfmdr1 whereas AQ resistance did not [67] . However, when CQR strain K1 was selected against halofantrine it did not result in MQ resistance or amplification of pfmdr1 [68] . In a more recent study, which used allelic exchange of pfmdr to probe these questions, incorporation of pfmdr1 7G8 polymorphisms into a CQS strain not previously exposed to a drug had no effect on CQ resistance, but incorporating wild-type pfmdr1 into a CQR strain expressing mutant pfmdr1 did decrease the level of resistance by half [58] . CQS strains expressing mutant pfmdr1 alleles showed some mild QN resistance and altered sensitivity to MQ [58] . Variations on this theme have also been described by Fidock and colleagues [59] . Collectively, these data suggest that PfMDR1 effects are subtle and strain-specific. This brings us to our current understanding: it seems unlikely that mutations in pfmdr1 confer CQ resistance in and of themselves [69] , but they (or overexpression of certain isoforms) provide an important modulatory effect [70] .