Acetylation and deacetylation of histones play important roles in transcription regulation, cell cycle progression and development events. The steady state Status of histone acetylation is controlled by a dynamic equilibrium between competing histone acetylase and cleacetylase (HDAC). We have used long PfHDAC-1 double-stranded (ds)RNA to interfere with its cognate mRNA expression and determined the effect on malaria parasite growth and development. Chloroquine- and pyrimethamine-resistant Plasmodium falciparum H strain was exposed to 1-25 mu g of dsRNA/ml ofculture for 48 h and growth was determined by [H-3]-hypoxanthine incorporation and microscopic examination. Parasite culture treated with 10 mu g/ml pfHDAC-1 dsRNA exhibited 47% growth inhibition when compared with either untreated control or culture treated with an unrelated dsRNA. PfHDAC-1 dsRNA specifically blocked maturation of trophozoite to schizont stages and decreased PfHDAC-1 transcript 44% in treated trophozoites. These results indicate the potential of HDAC-1 as a target for development of novel antimalarials. (C) 2009 Elsevier Inc. All rights reserved.