The unstable hemoglobins are characterized by a focal amino acid mutation that permits hemoglobin denaturation under certain conditions (e.g., heat or oxidation), with the formation of Heinz bodies. There are several different abnormalities, and either the alpha or beta hemoglobin chain may be affected. Unstable hemoglobin variants are rare; the best known are Hb-Kцln, Hb-Zurich, and Hb-Gun Hill. They are usually inherited as autosomal dominant traits. Depending on the hemoglobin variant, clinical and laboratory evidence of hemolytic anemia varies from normality to severe hemolytic disease. In some types that normally are subclinical, such as Hb-Kцln and Hb-Zurich, hemolysis may be precipitated by infection or oxidizing medications. Laboratory diagnosis is accomplished with a Heinz body test; if the results are positive for hemolytic disease, a heat stability test or isopropanol precipitation test is called for. In those patients with acute hemolytic episodes, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency may have to be differentiated. Heinz body formation is not specific for the unstable hemoglobins but may appear in patients with G-6-PD or certain other RBC enzyme defects when hemolysis is precipitated by chemicals and in alpha or beta thalassemia trait.