EGRET, the high-energy γ-ray telescope on the Compton Gamma-Ray Observatory, has the sensitivity, angular resolution, and background rejection necessary to study diffuse γ-ray emission from the interstellar medium (ISM). High-energy γ rays produced in cosmic-ray (CR) interactions in the ISM can be used to determine the CR density and calibrate the CO line as a tracer of molecular mass. Dominant production mechanisms for γ rays of energies ∼30 MeV–30 GeV are the decay of pions produced in collisions of CR protons with ambient matter and Bremsstrahlung scattering of CR electrons.