By means of double-diffusion precipitation tests in agarose gel with selected infectious mononucleosis (IM) sera, an antigen was detected in sera of patients with syphilis and leprosy. Of 378 syphilis sera tested 39 (10.3%) and of 36 leprosy sera 7 (19.4%) gave positive results. Sera of patients with various other diseases were negative. This antigen was demonstrable in sera of patients with both early and late syphilis and was shown to be unrelated to cardiolipin. Absorption studies of the IM sera with bovine and sheep erythrocytes and guinea pig tissues revealed that this antigen was identical with or closely related to the previously described B antigen of the Paul-Bunnell (P-B) antigenic complex and distinct from heterophile antigens of Hanganutziu-Deicher (H-D) and of Forssman specificity. However, 2 of 89 syphilis sera without the P-B antigen were shown to contain antigen(s) of H-D specificity. None of the syphilis or the leprosy sera contained P-B antibodies, but H-D antibodies were found in 13% of syphilis sera.