Two omega-3 fatty acids present in fish oil are effective inhibitors of some models of mammary and colon tumorigenesis in rodents. The present studies were conducted to determine if eicosapentaenoic and docosahexaenoic acids can modify the growth of DU-145 human prostatic tumor cells in nude mice. Two experimental diets tested contained either 23.52% corn oil or 20.52% fish oil, plus 3% corn oil (w/w). In the fish oil-fed group of mice: (a) tumor growth was significantly inhibited; (b) tumor cells in histological sections were smaller but more connective tissue was present; (c) immunochemical staining for human prostatic acid phosphatase was less intense, and (d) tumor content of PGE2 was smaller than in the 23.52% corn oil-fed group. Fatty acid composition of phosphoglyceride and neutral lipid fractions of liver, prostate, and tumor tissue reflect the dietary intake of omega-3 and omega-6 fatty acids. These results are consistent with a role for omega-3 fatty acids in the inhibition of growth of human prostatic tumor cells in nude mice by dietary modification.