The review of antimalarial pharmacology and the examination of results in recent studies of malaria in Vietnam revealed that (1) quinoline derivatives have multiple actions which include interference with nucleic acid replication and glucose metabolism; (2) sulfonamides and sulfones competitively antagonize aminobenzoic acid (PABA); and (3) folic acid reductase inhibitors interfere with the conversion of folic acid to folinic acid. No single agent produced satisfactory cure rates in recent trials with malaria in Vietnam. A combination of quinine and pyrimethamine appeared to give additive results. A combination of pyrimethamine and a sulfonamide gave superior results consistent with their proved synergism. A combination therapy of a long-acting sulfonamide with pyrimethamine, possibly with the addition of quinine, is recommended as the most rational therapy at this time.