Previous reports from our laboratory have shown that thyroid hormones induce changes in the fluidity and permeability of phospholipid bilayers and modify the transmembrane dipolar organization according to their iodine content. The interactions of T2, T3, and T4 with a model membrane of dilauroylphosphatidylcholine in the liquid-crystalline phase were analyzed by confocal Raman spectroscopy. Insights into the nature of the hormone effects on the membrane properties, as well as the structural adaptations of the hormones in response to the lipid environment were derived from the spectral changes. The series of progressive iodine substituents on the ring-β allowed us to correlate the hormone effects according to the number and the orientation of the iodine atoms. T4 was responsible for producing the highest alteration in the hydrophobic region of the membrane. Copyright © 2012 John Wiley & Sons, Ltd.