An Australian expatriate on regular weekly antimalarial prophylaxis with chloroquine base and Maloprim developed symptomatic Plasmodium vivax infection which failed to respond adequately to 600 mg of chloroquine base. More ominously, a resident of the Highlands region of Papua New Guinea contracted vivax malaria which failed to be cleared by 2400 mg chloroquine base administered over 4 d. Both patients had achieved appropriate blood and plasma concentrations of chloroquine after treatment. Chloroquine-resistant P. vivax is now a clinical fact in Papua New Guinea.