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CI-564 (Dapolar®), a mixture of cycloguanil pamoate and diacetyldiamino-diphenylsulfone (DADDS), was used as a repository antimalarial in a test of its suppressive and prophylactic effectiveness. Children of 12 years of age or less, in an area of endemic malaria in the Amazon valley in Brazil, were treated; CI-564 was given to 300 children and CI-564 plus amodiaquin to 300 children; 300 other children to whom no suppressive medication was given served as a control. Initial CI-564 injections were repeated twice at 4-month intervals, and children who had also received amodiaquin were given single doses of this drug with the second and third injections. In the group that received CI-564, ring forms of Plasmodium falciparum disappeared from the peripheral blood within 3 days, and all circulating forms of Plasmodium vivax within 7 days. Throughout the trial there was no significant difference between the treated groups in the prevalence of parasitemia, while there was significantly more parasitemia in the control group. CI-564 alone or with amodiaquin exerted a significant prophylactic effect against both P. falciparum and P. vivax infections. During the 4-month follow-up periods between injections, there were 22 instances of breakthrough by P. falciparum, of which 18 (81%) occurred 90 to 120 days after the previous injection. No breakthrough by P. vivax occurred before Day 90, while there were 39 failures thereafter. Local reactions to CI-564 injections were moderate and transitory, induration and tenderness being most common. There were no allergic reactions after the second and third injections. We conclude that CI-564 can be a practical prophylactic against malaria in suitable situations.