Previously reported cases of Histoplasma capsulatum infection of prosthetic heart valves have been first diagnosed at autopsy. A patient had an H capsulatum infection that was diagnosed by serologic means 1 1/2 years before involvement of the patient's prosthetic mitral valve was found at surgery. Numerous previous attempts to demonstrate organisms by culture and histologic study of bone marrow and liver biopsy specimens were unsuccessful. Various serologic tests were used in the diagnosis and evaluation of treatment of H capsulatum endocarditis. The management of this case was compared with 29 other previously reported cases of endocarditis caused by H capsulatum.