The three-dimensional high-resolution structure of rhodopsin is unknown, as is the case for almost all integral membrane patients. As part of an alternative approach to determine of membrane protein structure, we are pursuing the structure of cytoplasmic domains of this G-protein receptor. A peptide, rhoIII, with the sequence of the third cytoplasmic loop of bovine rhodopsin was synthesized. This soluble peptide was biologically active, inhibiting the light-stimulated activation of the rod cell phosphodiesterase by rhodopsin in rod outer segment disks. Therefore rhoIII likely contains structural elements characteristic of native rhodopsin. The structure of rhoIII was determined by H nuclear magnetic resonance. A defined structure was obtained for about 70% of rhoIII. A model of a turn-helix-turn motif could then be proposed for the third cytoplasmic loop of rhodopsin, which suggested a molecular switch for activation of the G-protein by the receptor.