Because anticancer immunity declines progressively with tumor growth, a major focus of current research in tumor immunology is the development of means to stimulate the host immune system. This study determined the effects of dietary long-chain (n-3) fatty acids and tumor burden on immune cell phospholipid composition and membrane-mediated immune defense in rats implanted with the R3230AC mammary adenocarcinoma. Fischer 344 rats (145 +/- 2 g) were fed one of two semipurified diets (20 g/100 g fat) for 21 d before and 17 d after tumor implantation. Diets provided long-chain (n-3) fatty acids at 0 or 50 g/kg of total fat. Mammary tumor growth was 31% lower (P = 0.1) in rats fed long-chain (n-3) fatty acids. Dietary long-chain (n-3) fatty acids had beneficial effects on several host immune defenses, including activation of CD8(+) T cells and type-1 cytokine (interferon-gamma and tumor necrosis factor-alpha) production (P < 0.05). Upregulated immune function in tumor-bearing rats fed the high (n-3) diet occurred concurrently with specific changes in the major membrane phospholipids phosphatidylcholine and phosphatidylethanolamine in high (n-3)-fed rats. Because membrane composition plays a critical role in immune function, additional work is needed to determine the relationship between alterations in the phospholipid composition of immune cells during cancer and subsequent upregulation of host defense in the tumor-bearing state.