This study was undertaken to evaluate the protective and therapeutic efficacy of pyrimethamine (Daraprim) against Chesson strain Plasmodium vivax in human volunteers. The drug was highly effective as a suppressive agent, 0.8 to 25 mg. gave complete protection during drug administration; it was less efficient when used for therapy of acute attacks. Pyrimethamine does not appear to be a true causal prophylactic although prolonged delays before patent parasitemia suggested some deleterious effect against early tissue stages of the parasite. Weekly administration of the drug for 8 or more weeks resulted in suppressive cure of many infections. Probably the greatest usefulness of the drug will be for routine suppression.