The membrane response in terms of changes in the lipid correlation length and lipid chain distance addressed above can neither reveal the insertion depth of a particular peptide side chain nor does it allow distinguishing between a membrane-spanning state or insertion perpendicular to the membrane normal. FRET experiments (parallax analysis) are well suited to studying membrane proteins in vivo but are often limited in resolution caused by large Förster radii of the fluorescence probes. In contrast, X-ray reflectivity in combination with contrast variation by heavy atom labeling can provide structural constraints down to subnanometer resolution for fluid or condensed peptide/lipid samples. For a fast in-house approach, the analysis of the electron density difference is a unique method to obtain highly resolved information about the localization of a certain structural element within a lipid bilayer (Fig. 7) . As shown in previous studies for the double helical homodimer 1, this method is even capable of producing evidence of a transmembrane peptide orientation within the lipid bilayer via iodine labeling at several positions (Küsel et al. 2007 ). With the iodine-labeling approach, the alignment of the membrane-spanning helical hairpin formed by the severe acute respiratory syndrome (SARS) coronavirus E protein could be elucidated by localizing the Phe23 adjacent to the lipid headgroup region (Arbely et al. 2004; Khattari et al. 2006a, b) . Instead of determining the label position by a comparison of the deduced electron densities q(z) resulting from unlabeled and labeled samples, this can also be accomplished using an isomorphic sample and applying different photon energies (Khattari et al. 2005) .