Total heme catabolism has been studied through measurement of the endogenous production of carbon monoxide (VCO) in 8 patients with hemolysis, 7 with hypoproliferative anemia, 10 with refractory anemia and hypercellular bone marrow and 7 with splenomegaly, 6 of whom had myeloid metaplasia. Simultaneously, catabolism of circulating red cell hemoglobin heme (Vheme-c) was measured through labelling of the red cells with 51Cr, and the VCA/Vheme-c ratio was calculated for each patient. From a control group it was calculated that this ratio should vary around 1.5. Since no isotope studies were performed in the control group, no range could be defined. Among patients with hemolysis the VCO/Vheme-c ratio was found to vary between 1.3 and 1.8 except in 2 cases of paroxysmal nocturnal hemoglobinuria (PNH) and PNH?, respectively, in whom the ratios were found to be 0.6 and 0.7 suggesting some heme catabolism without corresponding CO formation. In the hypoproliferative group the ratio varied between 1.2 and 1.8 except in one patient treated with androgens, in whom the ratio was found to be 2.9, suggesting increased extraerythrocytic heme turnover. In patients with myeloid metaplasia the ratio varied between 1.3 and 1.8. On the other hand, the ratio varied getween 2.4 and 3.0 among patients with refractory anemia and hypercellular bone marrow, thus confirming earlier findings that in this type of anemia turnover of bone marrow heme is markedly increased. A significant correlation was found between VCO and initial morning COHb%(r equals 0.84). The conclusions drawn are (a) that Vheme-c sometimes represents less than 50% of total heme turnover and (b) that COHb and/or VCO reflect total heme turnover except in patients with blood loss or intravascular hemolysis with hemoglobinuria.