Histamine has many regulatory activities and is well recognised for its importance in allergic and inflammatory disorders. Recently, histamine has been implicated in the pathophysiological processes of both rheumatoid and osteoarthritis, where human articular chondrocytes (HACs) and rheumatoid synovial fibroblasts (RSFs) are reported to express histamine receptors. This study has demonstrated H(1) and H(2) histamine receptors using immunohistochemistry on HACs and RSFs in vitro and has compared the effects of histamine (20 microM) on both cell types with regard to the production of matrix metalloproteinases (MMPs-1, -3, -8 and -13), the proinflammatory cytokine tumour necrosis factor alpha (TNFalpha) and prostaglandin E(2) (PGE(2)). On incubation with histamine, HACs showed increased production of MMP-3, MMP-13, TNFalpha and PGE(2) (statistical significance P=0.02, 0.005, 0.008 and 0.03, respectively, student's t-test), but MMP-1 expression was unaffected. In contrast, the RSF showed a histamine-induced increase in MMP-1 ( P=0.028) and an approximate 10-fold level of MMP-3 and PGE(2) release over that of HACs, each being stimulated by histamine ( P=0.02 and 0.032, respectively, student's t-test). However, MMP-8, MMP-13 and TNFalpha were not detected for RSF cultures. Our results show that histamine modifies the behaviour of both HACs and RSFs in vitro, but different effects were observed for the production of specific MMPs and TNFalpha by the two cell types.