This study evaluated the influence of cytokines and growth factors on the production of matrix metalloproteinase-2 (MMP-2, 72-kDa type IV collagenase, gelatinase A) and invasion of the human renal cell carcinoma (HRCC) cell line KG-2. The cells were treated with cytokines and growth factors, and the gelatiolytic activity and in vitro invasion were examined. Basic fibroblast growth factor (bFGF) stimulated MMP-2 production by KG-2 cells to 2.0-, 4.84- and 4.53-fold that of the untreated group at 0.1, 1.0 and 10 ng/ml, respectively. Transforming growth factor-beta1 (TGF-beta1) at very low concentrations of 10 pg/ml and 100 pg/ml stimulated enzyme production in KG-2 cells by 1.74- and 2.83-fold, respectively. In contrast, interferon-gamma (IFN-gamma) decreased MMP-2 production by KG-2 cells at 10 and 100 U/ml to 69% and 41% of the level in the untreated group, respectively. At those concentrations, IFN-gamma did not cause cytostasis in KG-2 cells. Moreover, bFGF and TGF-beta1 (low concentrations) stimulated in vitro invasion of KG-2 cells, but IFN-gamma decreased the invasive activity, which was well correlated with the levels of MMP-2. However, the expression of MMP-2 mRNA of KG-2 cells treated with 10 ng/ml bFGF, 100 pg/ml TGF-beta1 and 100 U/ml IFN-gamma was shown to be 3.8-, 3.4- and 0.7-fold, respectively, those in untreated groups. Thus the production of MMP-2 in HRCC was influenced by cytokines and growth factors, and MMP-2 plays an important role in the invasion and metastasis of certain types of HRCC.