The tumour stroma represents the microenvironment of the tumor cells, and is an important determinant of tumour malignancy. It can promote both tumour progression and metastasis. The tumor-associated stromal cells (myofibroblasts, macrophages, and endothelial cells) are strongly influenced by a variety of mediators produced by tumor cells. Among these, TGF-β1 is a growth factor with a strong antiproliferative effects on normal epithelial cells, but a potent stimulator of mesenchymal cell proliferation. On tumour cells its proliferative effect is variable ranging from inhibition to stimulation of growth. Additionally, TGF-β1 induces a myofibroblastic differentiation of fibroblasts, and it suppresses cytotoxicity of tumor-associated macrophages. In this study we have investigated the growth properties of a TGF-β1-producing colorectal carcinoma cell line (HRT-18) after transfection with an anti-TGF-β1 ribozyme. A cell clone with reduced TGF-β1 expression was transplanted into a xenograft-SCID mouse model. The tumour cells were also cocultured with human macrophages to analyze cytotoxicity. TGF-β1 inhibition was associated with an increased histological differentiation and a delayed tumour growth. The ROI-suppressing effect of tumor cells on macrophages was significantly reduced in ribozym-transfected cells which was found to be associated with reduced tumor cell growth under these conditions. Therefore, these data support the idea that TGF-inhibitors are useful in the therapy of colorectal carcinoma.