The 115-residue protein CM2 from Influenza C virus has been recently characterized as a tetrameric integral membrane glycoprotein. Infrared spectroscopy and site-directed infrared dichroism were utilized here to determine its transmembrane structure. The transmembrane domain of CM2 is α- helical, and the helices are tilted by β = (14.6 ± 3.0)°from the membrane normal. The rotational pitch angle about the helix axis ω for the 1-13C- labeled residues Gly59 and Leu66 is ω = (218 ± 17)°, where ω is defined as zero for a residue pointing in the direction of the helix tilt. A detailed structure was obtained from a global molecular dynamics search utilizing the orientational data as an energy refinement term. The structure consists of a left-handed coiled-coil with a helix crossing angle of Ω = 16°. The putative transmembrane pore is occluded by the residue Met65. In addition hydrogen/deuterium exchange experiments show that the core is not accessible to water.