Efficient synthesis of 11-Z-retinals labeled with ²H at the C5, C9, or C13 methyl groups is described. The ²H-labeled retinals were used to regenerate the visual pigment rhodopsin for structural investigations. Solid-state ²H NMR data provided the orientation of retinal within the rhodopsin binding pocket as well as its conformation. Extension of the approach to other membrane receptors can yield knowledge of their mechanisms of activation as a guide for ligand-based drug design.