The detection of single iodine labels via difference analysis usually requires high peptide-to-lipid ratios in the range of P/L & 1/10 ( Arbely et al. 2004; Küsel et al. 2007) . With the synthesis of the novel double iodinated amino acid building block Fmoc-5,5-diiodoalyllglycine-OH, the use of an enhanced in-house reflectivity set up including substrate sizes of 15 9 25 mm and the addition of 5 mol% cholesterol to the lipid phase enabled recording up to seven lamellar orders from samples with a P/L = 1/50. The analysis of the electron density difference profiles then allowed for the determination of the iodine positions with high accuracy (Schneggenburger et al. 2009 ). Even for the Fmoc-Phe(4-I)-OH single label, P/L ratios of 1/50 turned out to be sufficient. Therefore, in-house reflectivity studies and anomalous reflectivity using synchrotron radiation were both performed at P/L = 1/50. Three differentially labeled peptide species, 5, 7, and 8 (Fig. 8) , were used to test for a transmembrane orientation. To avoid beam damage during anomalous reflectivity experiments, the respective curves were solely scanned around the Bragg reflections.