AbstractXenograft valves of glutaraldehyde‐treated bovine pericardial tissue have been claimed to be an excellent choice for the replacement of malfunctioning human heart valves. These valves exhibit low thrombogenicity, hemodynamic function, and transvalvular gradients superior to their mechanical and tissue counterparts. However, there are differences of opinion concerning the immunogenic properties of these valvular devices. This study was conducted to evaluate the immune reactivity of such implants. Data obtained indicated that whole xenograft sections of both untreated and treated valvular tissue remain immunogenic following initial and secondary subcutaneous implantations in rabbits. Homologous and cross‐reacting antibodies were detected by means of indirect hemagglutination test 30 days after initial implantation of the grafts. Presence of cellular immune response as judged by skin reaction and leukocyte migration inhibition tests indicated that glutaraldehyde treatment of tissues does not destroy cellular immunity. Data obtained also suggest that chemical modification of such implants by glutaraldehyde probably alters, but does not abolish some antigenic determinant sites on the tissue surface. Glutaraldehyde treatment of bovine pericardial tissue does not render the tissue immunologically in