Drug resistance in Plasmodium falciparum has turned into a major problem throughout the malaria endemic regions of the world. Surveillance of antimalarial drug resistance is therefore essential for early changes in drug policies. In the course of this first major application of the new field-deployable histidine-rich protein 2 (HRP2) in vitro drug sensitivity assay, we investigated the current status of drug sensitivity to the standard antimalarial drugs dihydroartemisinin, mefloquine, quinine, and chloroquine in an area with an exceptionally high level of multidrug resistance in Thailand. The geometric mean of 50 and 90% inhibitory concentrations determined for 44 successfully tested samples by the HRP2 assay were comparable to earlier published results from the same area suggesting relatively little change in the local drug resistance pattern during the past years. The HRP2 field test was found to be highly sensitive and simple enough to be entirely performed in the field.