It is known, that decreasing of n-6 polyunsaturated fatty acids (PUFAs) content with simultaneous increasing of n-3 PUFAs in phospholipides of cellular membranes lead to cardioprotection, at the same time some controversial data exist. Therefore, investigation of mechanisms responsible for the protective effect n-3 PUFA has an important value. The purpose of this work was to investigate the effect of phospholipid membrane modification by n-3 PUFA on reactivity of the heart to adrenergic influences, lipid peroxidation (LPO) and nitric oxide (NO) production. RESULTS: It was shown, that addition of n-3 PUFA to the diet decreased n-6 PUFA content with subsequent reduction of TxB2 and LTC4 content and also increased n-3 PUFA content in cardiac tissue. The inotropic and chronotropic responses on norepinephrine (NE) were significantly less expressed after membrane modification. Inclusion of n-3 PUFA into the diet limited LPO through inhibition free radicals production in myocardial tissue. Release of nitrite was enhanced by n-3 PUFA supplementation. These data suggest that modification of phospholipid membrane composition by n-3 PUFA may attenuate cardiovascular responses to stress. CONCLUSION: Fish oil n-3 PUFAs have cardioprotective effects, decrease cardiovascular reactivity to adrenergic influence, limited LPO and enhances NO generation.