Periprosthetic osteolysis depends on the biological activity of wear particles, but there is little known about the distribution of polyethylene wear particles (PE) in the surrounding joint tissue. The purpose of this study was to examine the localisation of wear particles of six different PEs, including four crosslinked polyethylenes (XPE), as well as their biological activity in the murine knee. Material and Methods. Wear particles of 4 XPE- and 2 UHMWPE-inserts were isolated (knee joint simulator). For all groups the particles were similar in size and shape (mean diameter 0.3–05μm; 20nm-nucleopore-filter; ISO; n = 100.000).56 female Balb/c mice were randomly assigned to six treatment groups and one control group: control (PBS), XPE1 (3×30 kGy Gamma, annealed/sequential irradiated), XPE2 (95 kGy E-beam, remelted), XPE3 (65 kGy E-beam, remelted), XPE 4 (50 kGy Gamma, remelted), UHMWPE 1, UHMWPE 2. 50 μl of each particle suspension [(0.1% vol/vol (particle volume/PBS volume) after removal of endotoxin] were injected into the left knee joint. After 1 week the mice were killed and a histological and immunhistochemical analysis of the knee joints was done (IL-1, TNF-, ICAM-1). For the immunhistochemistry the articular cartilage, the bone marrow and the synovial membrane were evaluated semiquantitatively (Kruskal-Wallis test; all pairwise multiple comparison procedure; Bonferoni correction; significance level: p<0.05). Results. All groups showed a thickened synovial layer with an increased cellular infiltration. The particles of XPE 1 and 2 were localised in the bone marrow as well as in the joint space. In contrast, the particles of XPE 3 and 4 were distributed in the synovial layer and in the bone marrow as well, but not in the joint space. The UHMWPE1 particles were mainly located in the bone marrow and joint space while the UHMWPE2 particles were mainly found in the bone marrow and the synovial layer. For all PE groups there was a higher cytokine expression compaired to control (p<0.0024) without any differences between the groups (bone marrow/synovial layer). The chondrocytes in the groups with XPE 1- and XPE 2-particles expressed more TNF- than in the control group and the other treatment groups (p = 0.000). Conclusion. XPEs lead to a similar inflammatory reaction in vivo compared to conventional polyethylenes. The high TNF- expression in the articular cartilage (groups XPE 1 and 2) might be explained by the localisation of the wear particles in the joint space in direct contact with the chondrocytes. Long-term studies are necessary to analyse the effects of different wear particle distributions in the joint surrounding tissue after knee and hip replacement. Furthermore it has to be investigated, whether their distribution in the joint space or their transport into the bone marrow is responsible for the level of the chronic inflammatory reaction