Immunity against the blood stage of Plasmodium falciparum malaria is associated with protective-type antibodies of certain classes and subclasses. Field studies have demonstrated the differential regulation of various IgG subclasses depending on the dynamics of parasite transmission and on the immune status of the individuals tested. The intrinsic properties of each IgG subclass has a crucial role in protection, both because immunoglobulin levels are dependent on their production and clearance from blood and because antibodies are actively used for parasite clearance. In vitro models using B cells obtained from P. falciparum-immune adults have enabled study of the production of various antibody subclasses depending on the individual and on the antigens used. Ex vivo and in vitro observations from immune donors have helped to extend our understanding of the development and regulation of the antibody response and to design more effective vaccine strategies.