Reagent-dependent reactivity can be described as agglutination of red blood cells (RBCs) in serologic testing that is not related to the interaction of RBC antigens and antibodies that the test system is intended to detect. In other words, reagent-dependent reactivity results in false-positive agglutination reactions in serologic testing. These false-positive reactions can cause confusion in antigen typing and RBC antibody detection and identification procedures, and may result in delays in patient transfusion. It is imperative that reagent-dependent reactivity is recognized and resolved during the investigation of ABO discrepancies, positive RBC antibody screens and antibody identification panels, and crossmatch reactivity.