The capacity of a retro-inverso form of a 16-residue peptide from the Antennapedia homeodomain to be taken up by cultured neurones was tested. Like its homologue made of L-amino acids, it was rapidly internalised and distributed throughout the cytoplasm and even the cell nucleus. The amount of retro-inverso peptide in cells after incubation in culture medium was 3.4 times that of the L-peptide form. With a cholesteryl moiety attached to the C-terminus to increase its lipophilicity, the retro-inverso peptide was internalised 8 times better than the L-form. The greater efficiency of the peptidomimetic is probably due to the resistance to proteolytic degradation conferred by the D-amino acids, as the sequence contains two sites sensitive to neuronal endoproteases. The peptide might be the basis for development of system for delivering a variety of molecules into cells.