Summary Two cases of Plasmodium falciparum infections, apparently originating in Porto Velho, Brazil, which were not eliminated by the usual curative doses of chloroquine are documented. One patient received a total of 6.675 grams chloroquine base, including four regimens varying from 0.9 to 2.1 grams each, without eradicating the parasites. She was cured subsequently by a 10-day quinine treatment. The second patient received a total of 3.675 grams chloroquine base, including two courses of 1.5 grams each, without eradicating the infection. He was cured by a 5-day treatment totaling 3.1 grams of chloroquine. This study confirms the presence of chloroquine-resistant P. falciparum in Porto Velho, Brazil, the second area in South America where chloroquine-resistant strains have been reported.