Three recently isolated Thai strains of Plasmodium falciparum were tested in vitro for their response to pyrimethamine, sulfadoxine, and both compounds in combination. One isolate, FCK, was moderately tolerant to pyrimethamine whereas FCM3 and FCM5 were not affected by this compound at serum level, being 100 times less responsive than a sensitive strain from the Gambia when tested similarly. This low degree of response is evidently due to drug resistance. Sensitivity to sulfadoxine was low in the Thai isolates, but was also lower than expected in the Gambian strain. Possible causes of the poor response are discussed. Pyrimethamine in combination with sulfadoxine showed a synergistic effect; the effective doses were reduced by ten and three times, respectively.