Primaquine-an 8-aminoquinoline derivative-is one of the most effective drugs for use against the tissue stages of the malaria parasite. Unfortunately certain persons suffer from an inherited defect of metabolism which renders them susceptible to haemolysis after ingestion of the 8-aminoquinolines, certain other drugs and some vegetables. Susceptibility appears to be inherited by a partially dominant sex-linked gene of variable expression. In persons with full expression of this defect, intravascular haemolysis may be of such severity as to mimic blackwater fever.It has been shown that the haemolysis caused by daily doses of primaquine is self-limited, provided that such doses are not excessive, by virtue of the fact that the younger erythrocytes are relatively resistant to destruction by the drug.Therapeutic studies reported in the present paper indicate that the toxicity is markedly diminished by regimens requiring administration in weekly doses (together with the standard suppressive dose of chloroquine or one of its congeners) while its therapeutic effectiveness in the radical cure of Chesson vivax malaria is increased.A weekly dose of 45 mg primaquine proved highly effective against severe Chesson vivax infections when administered for eight weeks. It cured 90% of infections, yet did not produce clinically demonstrable haemolysis in primaquine-sensitive adult males with major expression of the haemolytic trait.