Fifty adult patients with two-dimensional echocardiograms (2DE) meeting standard diagnostic criteria for mitral valve prolapse (MVP) were studied to evaluate the significance of a positive 2DE by using a new morphologic grading system, a simplified method for annular measurement, and clinical data. Patients with mild (grade I) 2DE MVP differed significantly from those with moderate (grade II) to severe (grade III) 2DE MVP. Mild prolapse patients were predominantly female (p = 0.05) and younger (p less than 0.01). Atypical physical findings were associated with mild MVP while mitral insufficiency murmurs were associated with moderate to severe MVP (p less than 0.0025). When present, atypical chest pain and/or low-grade ventricular ectopy were associated with mild 2DE MVP, while pulmonary congestion, high-grade ectopy, and/or endocarditis were associated with moderate to severe 2DE MVP (p less than 0.001). Symptomatic moderate to severe 2DE MVP patients tended to have large annular dimensions. Additional echocardiographic characteristics of mild 2DE MVP included insensitivity of the parasternal long-axis 2DE view in its detection (p = 0.00002), predominance of anterior leaflet involvement in the apical 2DE view (p = 0.01), and absence of significant difference from age- and sex-matched control subjects in any annular dimension. In contrast, moderate to severe 2DE MVP showed highly significant differences from age- and sex-matched control subjects and from each other in all annular dimensions. Echocardiographically mild MVP defines a subgroup which differs quantitatively and clinically from more advanced morphologic variants. The use of mild 2DE MVP as a diagnostic criterion for MVP should be qualified as being "of questionable diagnostic significance." When present, with or without corroborative auscultatory findings, it may define a subgroup of prolapse at lower risk of significant clinical events or one that represents a normal echocardiographic variant. New grading and annular measurement methodologies provide additional tools for 2DE analysis of MVP with potentially important clinical and prognostic implications.