A new model for catalysis of human carbonic anhydrase II issuggested. The model is based on theX-ray structure of the hydrogen bond network in the catalyticsite. The outer part of the network is proposed to adjustthe pKa of the catalytic site to theexperimentally observed value of about 7.The inner part of the network is proposed to become a low-barrierhydrogen bond network in the transition state.The energy released in forming the low-barrier hydrogen bondnetwork is used to catalyze the interconversion of CO2 and HCO3-.The suggested molecular mechanism is consistent with thegenerally accepted kinetic schemefor human carbonic anhydrase II.