Antibodies targeting the N-terminal domain of ERFE decrease iron levels and alter blood parameters in thalassemic mice. Four-week-old male Hbb(th3/+) mice were treated intravenously with 5 mg/kg of IgG2A control antibody, anti-ERFE 15.1, or anti-ERFE 20.1, twice a week for 4 weeks. IgG2A-treated wild-type (WT) mice were used as control for basal levels. After 4 weeks of treatment, mice were killed for analysis of serum hepcidin (A), serum iron and transferrin saturation (B), liver and spleen non-heme iron (C), spleen to body weight ratio (D), and blood parameters (E). *P < .05; **P < .01; ***P < .001; ****P < .0001 using one-way analysis of variance followed by the Tukey test for differences between IgG2A-treated Hbb(th3/+) mice and anti–ERFE-treated mice. ^#P < .05, ^##P < .01, ^###P < .001, ^####P < .0001 using one-way analysis of variance followed by the Tukey test for differences between WT mice and Hbb(th3/+) mice. HCT, hematocrit; HGB, hemoglobin; MCV, mean corpuscular volume; RBC, red blood cells; RDW, red blood cell distribution width. n = 5-8 mice per group.