We applied a modified immunofluorescence and immunoperoxidase method, utilizing labeled Blastomyces dermatitidis antigens, to look for specific antibody-bearing B/plasma cells in the tissue infiltrates of blastomycosis lesions induced in hamsters. No specific anti-blastomyces antibodies were detectable by this method, although such antibodies were present in blood samples as demonstrated by routine immunodiffusion techniques. These studies suggest that humoral immune reactions do not play a major role in the pathogenesis of lesions of blastomycosis in hamsters.