Objectives: This study investigates the prevalence of drug-resistant malaria infection in Kuwait in patients with malaria infection to the two most important and primary antimalarial drugs, chloroquine and mefloquine. Study Subjects and Methods: In vitro screening of malarial parasites to chloroquine and mefloquine was done during 1994–1996 in all those cases who presented with malaria-like symptoms and had a parasite density of ≥1,000 asexual pure Plasmodium falciparum parasites per microlitre of blood and had not taken any antimalarial drugs during the last 3 weeks. Results: During 1987–1997 the total number of malaria cases detected ranged between 650 and 1,350 each year. More than 75% of the cases had Plasmodium vivax infection. The majority of these cases (>98%) were detected in individuals coming from various malaria-endemic areas to reside or work in Kuwait. Of the 575 cases tested for drug resistance 42 isolates (7.3%) were resistant to chloroquine (MIC >8 pmol) and 6 isolates (1.04%) were resistant to mefloquine (MIC >64 pmol). The 50% inhibitory concentrations were 2.7 and 4.8 pmol for chloroquine and mefloquine, respectively. All the 6 isolates that were resistant to mefloquine were also resistant to chloroquine. Chloroquine resistance was seen in patients from various malaria-endemic countries. Conclusion: To date no indigenous case of malaria has been detected in Kuwait, however, recent environmental and demographic changes in and around the State of Kuwait may threaten the present status of zero endemicity. In this study we show that 7.3% of the malaria isolates tested were resistant to chloroquine and 1.04% isolates were resistant to mefloquine.