The term mitral valve prolapse is used to describe either one of the pathophysiological mechanisms of mitral regurgitation or a distinct biological condition with a defined inherited basis, with or without mitral incompetence. In the former case, association with rheumatic fever is implied by the definition itself; in the latter it's questionable (rheumatic fever could act as an environmental factor in the expression of a genetically determined mitral valve prolapse). Three hundred and twenty patients with mitral valve prolapse, diagnosed as a primary one, were studied in order to assess the prevalence of a well-documented history of rheumatic fever: this resulted higher versus a control population (5.6% vs 0.9%-p < 0.01). The retrospective nature of the study does not allow a definite conclusion. Familial as well as long-term follow-up studies are necessary to better define the association between rheumatic fever and mitral valve prolapse; a potentially different prognosis, mainly accounting to the development of a clinically relevant mitral regurgitation in patients with mitral valve prolapse and previous rheumatic fever, has to be searched.