Three procedures for the removal of immunoglobulin G (IgG) from human serum were evaluated for their effectiveness in eliminating false-positive results caused by rheumatoid factor and in removing IgG from serum to reduce competing-IgG interference in IgM enzyme-linked immunosorbent assay (ELISA) testing. The procedures investigated employed two anti-human IgG diluents and a recombinant protein G-filled tube. The anti-human IgG was more effective than the protein G method in eliminating false-positive results caused by rheumatoid factor and removed 5.4% more IgG from serum samples in the normal range (< 1,700 mg/dl) and up to 16.4% more of the IgG from samples with elevated levels (> 1,700 mg/dl). The recombinant protein G removed less IgM than the anti-human IgG diluents; however, this difference did not affect the results of the ELISA. For these reasons, the in-house-developed anti-human IgG diluent proved to be the most effective and economical for IgM serological testing.