In seeking a sensitive indicator for quantitative assessment of hemolytic disease, we found a close dependence of red cell creatine level on cell age. Studies in 21 patients with steady-state hemolysis showed high correlation (r=0.89, p less than 0.001) between reticulocyte counts and red cell creatine levels. Excluding elevation of the creatine level as a variable epiphenomenon of increased erythropoietic activity, density separation of normal red cells revealed distinctly higher creatine levels in younger cells. The reticulocyte counts and creatine levels as quantitative predictors of hemolytic processes were compared: in severe hemolytic anemias (T50Cr less than 11 days), erythrocyte survival (T50Cr) correlated well with creatine levels (r = -0.86, p less than 0.01) and, to a lesser degree, with reticulocyte counts (r = -0.72, p less than 0.05). In milder disease (T50Cr greater than 11 days), however, no correlation existed between reticulocyte counts and T50Cr, whereas the creating levels correlated closely with T50Cr (r = -0.84, p less than 0.001). Thus, on the basis of our regression equations, useful estimation of red cell survival may be obtained from single measurements of erythrocyte creatine.