Whipple's disease is a systemic infection sometimes associated with cardiac manifestations. Recently, there has been an increase in the number of reported cases of Whipple's endocarditis. The purpose of our study was to describe this entity. Data from 35 well-described cases of Whipple's endocarditis were collected and compared with those of blood culture-positive endocarditis, Q fever endocarditis, and Bartonella endocarditis. Some patients with generalized Whipple's disease presented with cardiac involvement, among other symptoms. Others presented with a nonspecific, blood culture-negative endocarditis with no associated symptoms. In comparison with cases of endocarditis due to other causes, congestive heart failure, fever, and previous valvular disease were less frequently observed in the cases of Whipple's endocarditis. Without examination of the excised valves, the diagnosis of infective endocarditis could not have been confirmed in most cases. Treatment is not well established. Whipple's endocarditis is a specific entity involving minor inflammatory reactions and negative blood cultures, and its incidence is probably underestimated.