Porcine bioprosthetic heart valves are manufactured specifically for the Novacor left ventricular assist system (LVAS). The study aim was to examine structural changes in these valves in LVAS explanted from patients supported for a mean of 285 days (range: 37-1,293 days). Histologic sections from inflow and outflow valves from 13 patients (11 males, two females) were studied immunohistochemically. In the macroscopically normal inflow valves (11/13), fibrin and macrophages were deposited on the outflow surface, and IgG and complement proteins C1q, C3 had infiltrated the extracellular matrix (ECM). Disrupted collagen layers stained for IgG and C1q were seen in the spongiosa after 293 days and in the ventricularis after 1,293 days. Endocarditis had enhanced bioprosthetic valve degradation. Eleven of the 13 valves were macroscopically normal in the outflow position. Infiltration of fibrin, IgG and complement fraction into the ECM was weaker in the outflow valves (11/13) than in the inflow valves for up to 200 days. Degraded collagenous matrix with IgG and C1q deposits were detected in one clinically failed valve explanted at day 1,293. The structural changes outlined occur more rapidly in inflow valves than in outflow valves; these differences are most likely related to the additional mechanical stress placed on inflow valves.