Dietary fatty acids (FAs) may be involved in the carcinogenic process within the prostate gland and progression to clinically manifest disease. We have shown that growth of the androgen-unresponsive PC-3 human prostate cancer cell line is stimulated in vitro by the presence of linoleic acid (LA), an omega-6 polyunsaturated FA. The response was positively related to the FA concentration over the entire range examined (5-750 ng/ml). Conversely, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two omega-3 FAs present in fish oils, inhibited PC-3 cell growth in a dose-dependent manner; both were equally effective, with an approximately 65% reduction in growth occurring at a concentration of 2.0 micrograms/ml (P less than 0.001). The DU 145 human prostate cancer cell line, which is also androgen-unresponsive, showed no growth response to LA and was less susceptible to growth inhibition when cultured in the presence of omega-3 FAs. Growth experiments with indomethacin, esculetin, and piroxicam, pharmacological inhibitors of eicosanoid biosynthesis with differing sites of action, indicated that human prostate cancer cell growth requires intact metabolic pathways for both leukotriene and prostaglandin production.