The TRPV1 channel is an important molecular detectors of irritating compounds, elevated temperatures and other stimuli such as extracellular pH and divalent cations. Since these channels are regulated by several other compounds involved in signaling pathways related to pain and inflammation, their study has relevance in the clinical field. In spite of their obvious physiological importance, relatively little is known of their structure and molecular organization. TRP channels have so far been refractory to traditional structural analyses, such as X-ray protein crystallography and NMR. Among the structural approaches to date, there exists a low resolution structure determined by cryo-electron microscopy (Moiseenkova-Bell et al., 2008) and at least to molecular homology models based on the available structures from Kv channels. As an alternative approach, we have undertaken determinations of the oligomeric state and inter and intra subunit distances of the TRPV1 ion channel, using FRET (Fluorescence Resonance Energy Transfer) measurements. We have constructed several fluorescently-tagged channels using the pair of fluorescent proteins(FPs) eCFP/eYFP, were the fluorescent proteins have being inserted in the N- and/or C- termini of the protein. By means of co-expressing different combinations of these constructs in HEK 293 cells, we measured apparent FRET efficiencies using a spectral-FRET method (Zheng et al. 2002). We were able to determine that the most likely number of subunits in the functional TRPV1 channel is four. The distances between FPs at the C- termini are shorter than the distances between N- termini. This suggest that the N- termini are located in the periffery of the C-termini. We have also used FRET between a non-fluorescent membrane probe and the YFP constructs to determine the distance between the C and N termini and the plane of the membrane. These experiments provide us with a glimpse of the possible gross molecular architecture and organization of the TRPV1 channel. The distances are consistent with both N and C termini being intracellular and forming a large mas of the channel. Some of our measurements are summarized in the figure below.