Both drugs are antifolates; they inhibit the production of enzymes involved in the synthesis of folic acid within the parasites. Either drug by itself is only moderately effective in treating malaria, because the parasitePlasmodium falciparum may be able to use exogenous folic acid, i.e. folic acid which is present in the parasite's environment, while in combination, the two substances have a synergistic effect which outbalances that ability.
The combination is considered to be more effective in treating malaria caused by Plasmodium falciparum than that caused by Plasmodium vivax, for which chloroquine is considered more effective, though in the absence of a species-specific diagnosis the sulfadoxine-pyrimethamine combination may be indicated. Due to side effects, however, it is no longer recommended as a routine preventative, but only to treat serious malaria infections or to prevent them in areas where other drugs may not work.