We demonstrate in this study that the n-3 polyunsaturated fatty acids derived from fish oil, namely, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA), can increase levels of tissue inhibitors of metal loprotemase-1 (TIMP-1) in the renal cell carcinoma cell line caki-1 by 26% and 17.42% respectively. The result of this elevation in TIMP-1 levels is a reduction of 48.48% in caki-1 invasion through the basement membrane component matrigel when cells are treated with DHA. By inhibition of 2-series prostaglandin production, a similar increase in TIMP-1 was observed in caki-1 cells. We conclude that the polyunstaurated fatty acid DHA, a component of fish oil, is capable of significantly reducing the invasive profile of renal cell carcinoma, and that this reduction is regulated by levels of 2-series prostaglandin production. (C) 2005 Elsevier Inc. All rights reserved.