To determine how toremifene, an anti-oestrogen triphenylethylene derivate, reduces tumour mass, we investigated its modulation of TGF-1 and TNF-␣ in fibroma fibroblasts. Normal and fibroma fibroblasts, isolated from patients affected by Gardner's syndrome without or with fibroma manifestation, were cultured in vitro. Secretion of GAG, collagen and TGF-1 was increased in fibroma fibroblasts compared to healthy cells. The increase in TGF-1 secretion into the medium was associated with a parallel increase in TGF-1 gene expression and receptor number. Receptor cross-linking studies using radiolabelled TGF-1 revealed more receptors, particularly types I and II, in fibroma fibroblasts than in normal cells. Normal and fibroma fibroblasts did not synthesise TNF-␣, but they had TNF-␣ membrane receptors, as shown by TNF-␣ assay. TNF-␣ secreted by human monocytes, which may be present in the peritumoral area, increased cell proliferation and GAG accumulation and was, in turn, enhanced by TGF-1 treatment. Both growth factors increased angiogenesis, as shown by the CAM assay. Toremifene reduced TGF-1 secretion by fibroma fibroblasts and TNF-␣ secretion by monocytes, thus downregulating cell proliferation, ECM macromolecule accumulation and angiogenic progression. We hypothesise that increased TGF-1 gene expression and TGF-1 secretion in fibroma fibroblasts as well as the subsequent rise in TNF-␣ production by monocytes may facilitate fibroma growth and that toremifene inhibits autocrine and paracrine growth factor production.