Three standard antimalarial compounds were tested against trophozoite or sporozoite induced infections of the Panamanian Achiote strain of Plasmodium vivax in two species of monkeys. In Saimiri sciureus (24 subjects) and Aotus trivirgatus (11 subjects), parasite clearance from the peripheral blood averaged 3 days after initiating chloroquine therapy (total dose of 25 mg base/kg body weight over 3 days or single dose of 10 mg base/kg). Trophozoite induced infections were cured in all of 10 Saimiri and all of 6 Aotus, as indicated by the absence of relapses. Relapses did occur in 3 of 11 tests with Saimiri and 3 of 5 tests with Aotus against sporozoite induced infections. Subpatent periods ranged from 38 to 111 days among intact and splenectomized hosts. This is the first chemotherapeutic evidence for the persistence of exoerythrocytic stages of P. vivax in New World monkeys. Pyrimethamine (single dose of 1 mg/kg) cured trophozoite induced infections in all of five Saimiri hosts. Radical cure of sporozoite induced infections was accomplished in each of six trials with chloroquine (25 mg base/kg) plus primaquine (1 mg base/kg for 14 days). The primary attack or relapse was treated. These models warrant further investigation in chemotherapy.