The development of new effective antimalarial agents is urgently needed due to the ineffectiveness of current drug regimes on the most virulent human malaria parasite Plasmodium falciparum. Histone deacetylase and topoisomerase II of the malarial parasites have been proposed as potential new targets for antimalarial compounds. In this study, we report the result of using two long double-stranded RNA encoding a segment of the parasite histone deacetylase (pfHDAC) and topoisomerase II to interfere with the cognate messenger expression. Chloroquine- and pyrimethamineresistant P. falciparum K1 strain was exposed to pfHDAC or topoisomerase II dsRNA for 48 h and growth was determined by hypoxanthine incorporation assay. Exogeneously delivery of pfHDAC dsRNA between 1 and 200 nM significantly inhibited parasite growth up to 45% as compared with either untreated cultures or cultures treated with unrelated dsRNA (gfp) whichhad some inhibitory effect (314%). In addition, the decrease in parasite growth correlated with the decrease in levels of pfHDAC mRNA. Similar result was also observed with topoisomerase dsRNA.