Objective To investigate the feasibility of RNA interference(RNAi)strategy in mouse(embryonic stem)ES cells and study the possibility of RNAi in dermatological research.Methods Specific RNAi was introduced with EGFP gene as a target,either by in situ production of dsRNA from transient trans-fection of a plasmid harboring a547bp inverted repeat,or by direct transfection of dsRNA made by in vitro transcription.Gene silence of EGFP in EGFP-transgenic mouse was investigated by topical delivery of dsRNA.Results This longer dsRNA was capable of inducing a sequence-specific RNAi for the target gene in epi-some and in chromosome of ES cells.It was also shown that this sequence-specific RNAi was observed in EGFP-transgenic mouse by topical delivery of dsRNA.Conclusion These results suggest that ES cell possess RNAi activity by longer dsRNA.We first report the study on RNAi activity by topical delivery of specific dsRNA.Above findings offer a possibility to use dsRNAi for inhibition of gene expression in dermatological re-search.