The specificity of IgG anti‐F(ab′)2 antibodies was examined in unfractionated sera of patients with rheumatoid arthritis and also with affinity‐purified antibody preparations. Examination of the sera by an enzyme‐linked immunosorbent assay, using pooled human F(ab′)2 fragments absorbed to microtiter plates, revealed that IgG anti‐F(ab′)2 antibodies cross‐react with human and rabbit IgG and rabbit F(ab′)2. IgG anti‐F(ab′)2 antibodies were purified by affinity chromatography and, when tested by a fluid‐phase inhibition enzyme‐linked immunosorbent assay, were found to be of 2 types. One fraction, similar to pepsin agglutinator, reacted with human F(ab′)2 fragment alone. The other fraction was cross‐reactive with human IgG and yet failed to react with idiotopes on Fab or epitopes on Fc fragments. The IgG anti‐F(ab′)2 antibodies we purified had no reactivity toward a human immune complex prepared from tetanus toxoid and antitoxoid.