This report describes 11 cases of Plasmodium vivax infection of Colombian origin that relapsed 49-166 days following treatment with chloroquine or amodiquine (1.5 g in 3 days) plus primaquine (15 mg daily for 14 days) a regimen widely used to effect radical cure of infections with this parasite. Relapses occurred under conditions that precluded reinfection. The fact that most of the relapses occurred within the last two years suggest that P. vivax drug resistance may be developing in Colombia and possibly other regions of South America.