Radionuclides of the noble gases are extensively used to assess ventilation and blood flow in clinical and investigative studies. Xenon-133 is most commonly used but is not optimal for these in vivo studies. Xenon-125 has better physical characteristics and can be produced with a cyclotron by a 127I(p,3n)125Xe reaction; this reaction results in a maximum of 25 mCi/gm/cm2/muA-hr for 31-MeV protons. Under actual production conditions, 11 mCi/muA-hr were collected. Xenon-125 decays by electron capture with a 17.2-hr half-life and contributes less radiation per dose of radioactivity than 133Xe. The radiation dose to the lungs from 133Xe and 125Xe is 5.0 and 1.8 mrads/mCi-min, respectively. The radiation dose per usable photon for 125Xe is only 0.3 of 133Xe. The principal photons of 125Xe, 188 keV (55%) and 243 keV (29%), are more intense and are in an energy range that is more advantageous for imaging than the 81 keV (35%) of 133Xe. These physical properties of 125Xe result in better spatial resolution at the same information density and with less radioactivity administered to the patient. Phantom studies showed that 12.7-, 9.5-, and 6.4-mm lead bars were resolved with 125Xe using a 410- keV diverging collimator wheras only the 12.7- and 9.k-mm lead bars were resolved using 133Xe and either a 410-keV or 140keV diverging collimator.