Gross and histologic observations are described in 51 Hancock glutaraldehyde-preserved porcine heterograft bioprostheses from 41 patients: 33 valves from 25 patients had been in place for less than 2 months (early) and 18 valves from 17 patients were examined at later periods up to 75 months (late) after implantation. The major gross changes were cuspal thrombosis (5 bioprostheses) and cuspal degeneration (3 bioprostheses). Major histologic changes observed in 44 bioprostheses (26 early and 18 late) examined histologically were: (1) fibrin deposits on inflow and outflow surfaces of the cusps; (2) inflammatory cell infiltrates; (3) histiocyte deposition; (4) giant cell formation, and (5) focal disruption of the fibrocollagenous structure of the cusps. These observations indicate that porcine bioprostheses are not biologically inert in the human circulation. Valve failure, however, is rare at the implantation periods studied.