The effect of cyclosporin A (CsA) on prostaglandin E2 (PGE2) production in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-alpha) was studied. TNF-alpha (1-100 ng/ml) dose-dependently stimulated PGE2 formation in 24 h cultures. CsA (1-100 ng/ml) did not induce PGE2 formation itself but potentiated TNF-alpha induced PGE2 formation in gingival fibroblasts in a manner dependent on the concentrations of both CsA and TNF-alpha. TNF-alpha (10 ng/ml) stimulated the release of [3H]-arachidonic acid (AA) from prelabelled fibroblasts that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5-20 microM/ml) to the cells resulted in enhanced PGE2 formation that was not potentiated by CsA (100 ng/ml). Furthermore, CsA (100 ng/ml) did not further increase the level of cyclooxygenase-2 mRNA induced by TNF-alpha (10 ng/ml), although PGE2 formation was enhanced. The results indicate that CsA and TNF-alpha act in concert on PGE2 formation in gingival fibroblasts, which may be of importance in the pathogenesis of gingival overgrowth induced by the drug.