OBJECTIVE: To compare the sensitivity of artesunate-sensitive and artesunate-resistant P. falciparum to pyronaridine, mefloquine and quinine and to understand the effect of artesunte combined with the above-mentioned 3 drugs respectively on artesunate-resistant P. falciparum. METHODS: Rieckmann's in vitro miorotechnique was used. RESULTS: The ID50 values of pyronaride, mefloquine, quinine and artesunate were 59.0, 69.7, 283.8 and 9.6 nmol/L to artesunate-sensitive P. falciparum; the ID50 of the 4 drugs mentioned above were 170.6, 63.2, 272.4 and 85.1 nmol/L to the artesunate-resistant P. falciparum, respectively. In artesunate pyronaridine combination, the ID50 values were 1/3.7 (22.8/85.1) and 1/4.7 (36.6/170.6) of the 2 drugs singly used. In artesunate mefloquine combinaton, the ID95 is 1/125 (3.2/400) and 1/16 (80/128) of the 2 drugs singly used, respectively. CONCLUSION: The artesunate-resistant P. falciparum isolate has no cross resistance to mefloquine and quinine. When artesunate was used in combination with the 2 drugs mentioned above respectively, the efficacy proved to be enhanced.