This contribution reports on the interaction of ss-polynucleotides of various length and sequence with liposomal dispersions of anionic lipids. No appreciable structural and morphological variations were detected for POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-glycerol) liposomes, as expected from the high negative charge density both of liposomal surface and of the poly or oligonucleotide. Conversely, when similarly charged POPN nucleolipids (1-palmitoyl-2-oleoylphosphatidyl-nucleosides) were used, meaningful differences could be observed both on size and morphology of the mixed aggregates. The comparison with POPG/nucleic acids mixed systems points to the conclusion that the driving force for association of nucleolipid liposomes with nucleic acids can be ascribed to selective interactions at the polar head level which overcome electrostatic repulsion. Dynamic light scattering. Cryo-TEM and circular dichroism provided an ensemble of results where an interesting dependence on the polynucleotide base nature and contour length emerges. The extent of interaction can be modulated, in terms of size of the complexes, by choice of background buffer, ionic strength and polynucleotide length. (C) 2011 Elsevier Inc. All rights reserved.