Phlebotomy treatment, with removal of iron contained in the hemoglobin of red cells, is the only effective therapy for HH. Phlebotomy therapy relieves many of the symptoms of iron-mediated tissue damage and prevents progression to cirrhosis. However, published laboratory guidelines for monitoring phlebotomy therapy are based on retrospective data, and in general allow a moderate level of iron overload to persist during maintenance therapy. Since 1987, the DTM has piloted the use of the red cell mean corpuscular volume (MCV), in conjunction with the hemoglobin, as a prospective guide to phlebotomy therapy in a small cohort of HH patients. In contrast to other retrospectively-derived guidelines, this simple, inexpensive, physiologic method was found to be a precise indicator of iron-limited erythropoiesis, and could be easily applied to adjust the pace of phlebotomy and prevent excess iron reaccumulation.