The synovium of the osteoarthritic knee was investigated for pathological changes after high tibial osteotomy (HTO) in a prospective two-year follow-up study. The series included 11 osteoarthritic knees in 9 patients with a mean age of 57 +/- 8 years (range: 47 to 70 years). Synovial specimens were obtained from the medial part of the knee just above the medial meniscus at the time of HTO, and taken from a different medial portion from the initial biopsy at the time of removal of the internal fixation (mean interval: 21 +/- 4 months). Lining cell hyperplasia, villous hypertrophy, cell infiltration, and vascular proliferation, observed in the first biopsy specimens, were less discernible in the samples from the second biopsy, which were obtained at the time of the removal of the fixation device. Immunohistochemical staining of the specimens revealed that cartilage fragments positive for type 2 collagen were surrounded by proliferating lining cells at the time of osteotomy. These lining cells were predominantly stained with anti-CD68 antibody for macrophage lineage cells. The mean numbers of type 2 collagen-positive fragments and CD68-positive cells in the lining layer at HTO were 9.1 +/- 6.2 (3 to 26) and 30.8 +/- 11.0 (17 to 55) per high power field (x400), respectively, while they were 1.1 +/- 1.2 (0 to 4) (p < 0.005) and 14.8 +/- 4.7 (7 to 21) (p < 0.01), respectively, at the time of removal. The number of these cartilage fragments decreased markedly after correction of the varus deformity by HTO. In conclusion, the excessive pressure on the medial compartment of the osteoarthritic knee with a varus deformity can cause wearing of the articular cartilage and fragmentation. The cartilage fragments might stimulate macrophage lineage cells in the lining layer and might cause synovitis in osteoarthritis. After correction of the varus deformity by HTO, the synovitis subsided because there were fewer cartilage fragments and less wear.