The long-term effects of practical amounts of fish oil on plasma lipids and lipoprotein cholesterol levels, bleeding times, erythrocyte deformabilities, and plasma phospholipid fatty acid (FA) composition were investigated in this trial. Twenty-eight hyperlipidemic patients with elevated cholesterol and triglyceride (TG) levels were randomly assigned to take 3, 6, 9, or 12 capsules of fish oil daily for 6 months, providing 1.25-5 g of n-3 FAs per day. Baseline parameters were compared to values after 1 and 6 months of treatment, and after 1 month of washout. There were no statistically significant changes in total cholesterol levels at any dose. Both low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels tended to rise, resulting in an unchanged ratio of LDL-C to HDL-C. The TG and very-low-density-lipoprotein cholesterol (VLDL-C) levels decreased significantly with all but the lowest dose. Bleeding times were unaffected despite a nonsignificant 34% increase detected at the highest dose. Red blood cell deformability tended to increase with the two middle doses only. The EPA level in plasma phospholipids was strongly correlated with n-3 FA (FA) consumption. We conclude that long-term treatment of hyperlipidemic patients with practical intakes of n-3 FAs produced persistent reductions in TG levels and no change in the LDL-C/HDL-C ratio.