Tautomerization paths of 2(and 4)-hydroxypyridine (called here HP) to 2(and 4)-pyridone (called here PY) with water molecules were investigated by the use of density functional theory calculations. Potential energies were compared for a number of water molecules. The 2-HP molecule was found to be isomerized most readily and concertedly to the 2-PY one via proton relays with two water molecules. The reaction pattern is invariant even when outer water molecules are added. The 4-HP(H2O)(n) --> 4-PY(H2O)(n) reaction model did not give small activation energies. However, a reaction of (4-HP)(2)(H2O)(2) --> (4-PY)(2)(H2O)(2) was found to occur readily through a transient ion-pair intermediate. The conversion processes of (2-PY)(2) to the tautomerization reacting system were discussed. The hydrogen-bond directionality regulates the tautomerization paths.