In a group of 40 patients discharged from the hospital after mitral valve replacement with an Ionescu-Shiley pericardial xenograft from January, 1977, to December, 1980, seven instances of valve failure occurred. This unprecedented incidence of bioprosthetic dysfunction after mitral valve replacement with the Ionescu-Shiley pericardial xenograft led us to update the follow-up of our patients receiving this valve in the mitral position. The results of our survey showed, at 6 years postoperatively, an actuarial survival rate of 72%, an actuarial probability of being free from emboli of 62%, and an actuarial freedom from prosthetic failure of 60%. The explanted valves showed complete absence of the neoendothelial lining of the Dacron-covered frame and lesions resembling those observed in Ionescu-Shiley pericardial xenografts removed from our fatigue test system after a mean of 29 +/- 17 X 10(6) cycles. This similarity prompted a classification of tears occurring in the mitral Ionescu-Shiley pericardial xenograft, which is of extreme importance, since the clinical presentation and outcome of patients with a failing valve differs according to the type of rupture. The lesions of the cusp observed in clinical specimens were possibly related to the continuous trauma of the tissue against the bare Dacron cloth during closure of the valve. It is concluded that (1) actual durability and thrombogenicity of the Ionescu-Shiley pericardial xenograft in the mitral position needs to be carefully reassessed, (2) close follow-up of such patients by clinical and two-dimensional echocardiographic evaluation is advisable after the third postoperative year, and (3) failure of the mitral Ionescu-Shiley pericardial xenograft may occur suddenly, and awareness of this complication is the clue to prompt recognition and treatment of such patients.