S-Adenosyl-L-methionine (SAMe) is a naturally occurring compound involved in transmethylation and trans-sulphuration reactions. The administration of SAMe to patients with osteoarthritis (OA) seems to have a protective effect, although the mechanisms of its action are largely unknown. We have studied the effect of SAMe as a protective agent against the modifications induced by tumour necrosis factor alpha (TNF alpha) on synovial cell proliferation and extracellular matrix protein synthesis, two important hallmarks of progressive articular diseases. The stimulation of cells with 100 U/ml TNF alpha for 24 h decreased the proliferative rate (58 +/- 14% with TNF alpha vs basal 100%, P < 0.05), fibronectin (FN) mRNA expression (36 +/- 14% vs basal, P < 0.05) and FN synthesis (79 +/- 20% vs basal, P > 0.05). By contrast, TNF alpha raised total protein and proteoglycan synthesis (127 +/- 12% vs basal and 239 +/- 40% vs basal, respectively, P < 0.05). The addition of increasing concentrations of SAMe (10(-10)-10(-6) M) to synoviocytes incubated with TNF alpha reversed the effects induced by the cytokine, while SAMe alone did not modify significantly the metabolic processes studied. These results indicate that, in cultured synovial cells, SAMe restores basal conditions after cell damage elicited by TNF alpha stimulation.