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Inhibition of most of the expression of the cysteine proteinases of Entamoeba histolytica strain HM‐1: IMSS was successfully performed by transcription of ehcp5 antisense RNA using the promoter of ehg34, which encodes a L21 ribosomal protein of E. histolytica. We have generated a stable transfectant in which the overall level of cysteine proteinase activity is strongly reduced (≈ 90%). This transfectant has a normal growth rate in Diamond's TYI‐S‐33 medium, a cytopathic and haemolytic activity similar to the control HM‐1:IMSS pEhAct‐Neo transfectant but with a significantly lower phagocytic activity.