Fifty Panamanian patients with 69 attacks of Plasmodium falciparum malaria were treated with chloroquine and amodiaquine, 4-aminoquinoline drugs. The cure rate was only 22%. Failures were represented by relapses, persistence of the parasitemia, or an increase in the parasitemia following administration of the drug. Some cases were cured when subsequent attacks were treated with the same drug. The high failure rate of 78% indicates resistance. This is the first report of 4-aminoquinoline drug resistance in P. falciparum malaria in a country north of Colombia in the Western Hemisphere. Patients given quinine sulfate 2 grams daily for 10 days were cured.