Despite distinct advantages over mechanical cardiac valve prostheses, the use of bioprosthetic valves remains limited due to poor long-term durability, primarily as a result of tissue calcification. A novel anticalcification process, based on treatment of porcine bioprostheses with a derivative of oleic acid, has been developed by one of us (J.M.G.) (US Patent Number 4,976,733). This process employing 2-aminooleic acid (AOA) was tested in a juvenile sheep model. Terminal studies after a 20-week interval included hemodynamic, radiographic, morphologic, and quantitative tissue calcium analyses. All control valves (n = 4) had thickened, immobile, heavily calcified leaflets, whereas all AOA-treated valves (n = 8) were pliable and free of calcium deposits. Calculated valve orifice areas for controls (0.9 +/- 0.2 cm2) (mean +/- standard error of the mean) was less than for AOA-treated valves (2.0 +/- 0.3 cm2) (p less than 0.05). Radiographic calcification scores were greatly elevated in the control (25.5 +/- 5.6) versus AOA-treated valves (0.5 +/- 0.5) (p less than 0.002). In quantitative mineralization studies, the mean calcium content of the control leaflets was 129 +/- 21 milligrams per gram dry weight cusp tissue versus 7.7 +/- 5.8 mg/g for AOA-treated valves (p less than 0.001). Pathologic examination confirmed heavy calcification in the control leaflets, which was essentially absent in the AOA-treated leaflets. However, cuspal hematomas in areas of structural loosening and surface roughening were noted in AOA-treated valves. This anticalcification process dramatically reduced mineralization of porcine valve prostheses in this model.