Polyethylene glycol (PEG) is used as a potentiator of blood group antigen-antibody interactions. Although PEG is known to precipitate immunoglobulins, we could find no reports of this reagent entrapping red blood cells (RBCs) in irreversible clumps. The patient we describe here had hyperglobulinemia with a reversed albumin:globulin ratio and a diffuse immunoglobulin peak on serum protein electrophoresis. During preparation of serologic tests, a precipitate formed that entrapped the RBCs when PEG was added. Rapid recognition of this phenomenon could prevent delay in the selection of blood for transfusion by substituting PEG-indirect antiglobulin test (IAT) with another technique such as low-ionic-strength solution (LISS)-IAT, and by increasing the number of washes prior to addition of the antiglobulin reagent.