Chloroquine-resistance is associated with higher malaria mortality in children in Africa where the drug is still widely used. In sensitive strains the drug attacks hemoglobin digestion in the lysosome and prevents detoxification of hemin to hemozoin. Reduced drug uptake is responsible for resistance, which is incompletely associated with changes in lysosome membrane protein PGH1. The report discussed here gives evidence for the role of another lysosome membrane protein, PfCRT, where a change from lysine to threonine in a transmembrane domain determines the change to resistance. Other changes in PfCRT, and to some extent change(s) in PGH1, are believed to compensate for loss of fitness of the modified PfCRT.