The efficient delivery of short interfering RNAs (siRNAs) into cells provides a powerful approach to study cellular functions. SiRNAs were coupled to the membrane permeant peptides (MPPs) penetratin and transportan to improve their uptake by cells. Thiol-containing siRNAs corresponding to luciferase, or green fluorescent protein (GFP) transgenes, were synthesized and conjugated to penetratin or transportan via a disulfide bond that is labile in the reducing environment of the cytoplasm. These MPP-siRNAs efficiently reduced transient and stable expression of reporter transgenes in several mammalian cell types in a high proportion of cells, and demonstrated equivalent or better delivery characteristics than cationic liposomes with fewer manipulations.