Abstract: This report presents the effect of three antimalarial agents-chloroquine, piperaquine and hydroxypiperaquine-upon asexual erythrocytic forms of Plasmodium falciparum. An in vitro microtechnique was employed to assess the effect exerted on a strain of chloroquine-resistant P. falciparum (Cambodian I strain) compared with that on a strain of chloroquine sensitive P. falciparum (FCC-l/HN strain). The ED50 of chloroquine, piperaquine and hydroxypiperaquine against sensitive strain were 81, 59 and 56nM respectively after 48 hours cultivation, while the ED50 of these drugs against resistant strain were 563, 61 and 60nM respectively. The results obtained showed that the Cambodian strain was a 7-fold chloroquine-resistant strain and hadn't any significant cross resistance to piperaquine or hydroxypiperaquine. However, the resistance of this strain was unstable. Following in vitro cultivation without stimulation of chloroquine for 17 days, the degree of resistance decreased from 7 to 3.4 fold.