The lipemic effect of dietary fish oil vs. corn oil may be affected by the background composition of the diet. To investigate this theory, rats were fed diets containing either fish oil or corn oil and differing in the amount of fat and cholesterol and in the type of carbohydrate (sucrose vs. glucose) or protein (casein vs. soy protein). The hypotriglyceridemic effect of fish oil vs. corn oil was not influenced by the background composition of the diet. The hypocholesterolemic effect of fish oil was diminished by increasing the amount of coconut fat in the background diet at the expense of an isoenergetic amount of sucrose. With the use of high-cholesterol diets, no cholesterol-lowering effect of fish oil vs. corn oil was observed. This study suggests that the composition of the background diet should be considered when comparing the cholesterolemic effects of fish oil with other oils in various experiments.