Infective endocarditis is not a simple interaction between a microbial agent and a cardiac valve. For the infection of a non-bacterial thrombotic vegetation, predisposition is required which is at least partially operative by a decreased suppressor T cell activity. During infection, peripheral blood natural killer cell activity is decreased, but normalizes under anti-microbial therapy. Non-major histocompatibility complex-restricted lymphocytotoxicity to isolated heart cells can be present in one third of patients. Circulating immune complexes normalize during therapy. They may be the cause of many clinical symptoms of infective endocarditis. Anti-bacterial and also anti-sarcolemmal antibodies which are cross-reactive to the bacterium are secreted in a polyclonal immune response. Anti-sarcolemmal antibodies which are cytolytic in vitro in the presence of complement may partly explain the myocardial factor of heart failure in patients with only marginal valve incompetence due to the endocarditic vegetation.