Degeneration and loss of articular cartilage are the characteristic features of osteoarthritis (OA), with the appearance of fibrillations, cell clusters, matrix depletion, and changes in matrix composition all apparent. Histamine has a recognised role in allergic and inflammatory reactions, and is reported to affect several aspects of chondrocyte behaviour. The immunohistochemical (IHC) studies reported here have demonstrated histamine (H), both H1 and H2 receptors, and the histamine-producing enzyme histidine decarboxylase (HDC) in a variable proportion of human articular chondrocytes in OA cartilage specimens. Such observations were especially evident within the degenerative, superficial zone, and more so in late-stage disease. By contrast, "normal" age-matched cartilage specimens showed relatively little immunopositive staining for histamine and HDC. These findings strongly suggest that histamine and H-receptor expression by HAC in OA cartilage is potentially an important contributor to the atypical, aberrant phenotype of OA chondrocytes.