The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by ω3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chowad libitum were inoculated with 106 MAT-LyLu cells (n=14) or saline (n=9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumorbearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7–14 (difference by dietary group: NTB,P<0.001; TB,P<0.001). During days 14–21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB,P<0.003; TB,P=0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P=0.05) and mean food intake during the study (P=0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean ±SEM 58±10 g loss,P<0.001), but not in TB animals on fish oil diets (8±18 g loss,P=0.67). This positive effect of fish oil diets on carcass weight in TB animals was statistically significant (50±19 g,P<0.02), implicating that the fish oil enriched diet inhibited tumor-induced weight loss by more than 85%. No effect of fish oil diets on tumor growth was detected. In all TB animals, regardless of diet, hepatic [Pi]/adenosine triphosphate] ratios measured by31P magnetic resonance spectroscopy (MRS)in vivo andin vitro were elevated, and absolute concentrations of phosphocholine, glycerophosphocho-line, glycerophosphoethanolamine and glucose-6-phosphate as determined by31P MRSin vitro were reduced. Ultrastructural studies of liver tissue revealed increased numbers of mitochondria and increased amounts of endoplasmic reticulum in the host liver of TB animals, without differences between dietary group. In conclusion, fish oil supplementation partially inhibited MAT-LyLu tumor-induced cachexia, but did not prevent the majority of31P MRS-detectable alterations in host liver metabolism.