To investigate whether dietary linoleic acid inhibits lymphocyte proliferation, rabbits were fed diets containing 35% of the digestible energy (35 en%) as sunflower seed oil (25 en% linoleic acid) or palm oil (3.5 en% linoleic acid). No differences in the mitogen-induced proliferation of peripheral blood lymphocytes (PBL) or splenocytes or in the effect of sera on PBL proliferation were observed. To investigate whether the amount of dietary fat affects lymphocyte proliferation, rats were fed diets containing 10 or 35 en% as fat. No difference in the mitogen-induced proliferation of splenocytes was obtained. However, serum from fed rats but not from fasted rats of the 35 en% fat group inhibited splenocyte proliferation, in comparison with serum from rats of the 10 en% fat group. Removing chylomicrons from the sera did not affect proliferation. The very low density lipoprotein + chylomicron fraction of the plasma inhibited proliferation. The inhibition was stronger for the 35 en% fat group than for the 10 en% fat group and was increased by fasting. No systematic differences in the effects on proliferation were obtained with the low or high density lipoprotein fractions of both groups. Diets containing a high amount of linoleic acid do not inhibit lymphocyte proliferation. The amount of dietary fat might affect lymphocyte proliferation through one or more factors in the plasma.