The nucleoside monophosphate kinases, adenylate kinase (AK), guanylate kinase (GUK), and uridine monophosphate kinase (UMPK), were studied electrophoretically and quantitatively in density gradient fractions of human red cells from normal adults which contain red cells of differing mean age. The enzymes were found to differ both in their rates and patterns of decay and in secondary isozyme formation during the life of the red cell in the circulation. AK showed no appreciable enzyme decay and slight genetation of secondary isozymes; UMPK showed a rapid monophasic decline and no secondary isozyme formation; GUK showed intermediate overall loss of activity with a biphasic pattern of decay and marked secondary isozyme formation. A comparative study of the two common phenotypes of UMPK (UMPK 1 and UMPK 2-1) and of AK (AK 1 and AK 2-1) was made. The UMPK 2 isozyme showed a more rapid decay than the UMPK 1 isozyme, whereas no difference was observed between the AK 1 and AK 2 isozymes.