BACKGROUND: Rabbit erythrocyte stroma (RESt, Immucor) adsorption is often used to remove cold autoantibodies from patient samples to facilitate detection of underlying alloantibodies. However, reports in the literature show that adsorption of clinically significant alloantibodies can occur. A 2006 study by Storry and colleagues suggested that immunoglobulin (Ig)M antibodies are adsorbed by RESt regardless of antigen specificity. In our study, we further investigated the adsorption of IgM red blood cell alloantibodies by RESt. STUDY DESIGN AND METHODS: A total of 12 sera containing monoclonal IgM antibodies of various specificities (anti-D-Jk b , and -S) and titers, which were all shown to exhibit only IgM reactivity after dithiothreitol treatment, and two sera with polyclonal IgG (anti-Fy a and -K) were all adsorbed by RESt. Titers of unadsorbed, once-adsorbed, and twiceadsorbed IgM and IgG antibodies were determined in parallel. RESULTS: Ten of the 12 monoclonal IgM samples showed significant (more than fourfold) reduction in titer after RESt adsorptions. Both of the polyclonal IgG samples tested showed insignificant (fourfold or less) reduction in titer. CONCLUSIONS: RESt is known to effectively remove IgM cold autoantibodies. Our results show that monoclonal IgM alloantibodies are also frequently adsorbed by RESt with significant reduction in titer. Adsorption is variable and some IgM alloantibodies are not adsorbed. Further studies may elucidate the effect of RESt adsorption on IgG alloantibodies. Caution is needed when RESt is employed to remove interferences by cold autoantibodies in pretransfusion testing, and the risk of missed IgM alloantibodies must be considered.