Natural killer (NK) cells are a subset of cytotoxic lymphocytes found mainly in blood and the spleen. NK cells play a role in natural immunity to microbes, viruses and tumor cells and are involved in the rejection of grafts. The present study investigated the effects of diets containing oils rich in saturated fatty acids, mono-unsaturated fatty acids, n-6-poly-unsaturated fatty acids (PUFA) or n-3-PUFA on the NK cell activity and on the lymphokine-activated killer (LAK) cell activity of rat spleen lymphocytes. Weanling rats were fed for 10 weeks on a low-fat (LF) diet (approximately 2% fat by weight) or on 1 of 5 high-fat (HF) diets, which contained 20% (by weight) hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or menhaden (fish) oil (MO). Each of the HF diets suppressed the NK activity of freshly prepared spleen lymphocytes compared with the LF diet; cells from the MO-fed rats exhibited the lowest NK activity. Culture with IFN alpha for 3 h increased the NK activity of spleen lymphocytes from all animals, except those fed the OO diet; the increase in NK activity varied from 20% (LF) to 50% (MO). Although feeding the OO, EPO or MO diets resulted in lower IFN alpha-stimulated NK activity than that obtained by feeding the LF diet, the only consistent significant difference was the lower activity of the cells from the OO-fed rats compared with those from the LF-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)