The long-term metabolic effects of n-3 fatty acids were studied in patients with coronary artery disease. They were investigated before and 9 mo after bypass surgery. After postoperative randomization, 260 patients received 4 g fish-oil concentrate/d (approximately 3.4 g eicosapentaenoic and docosahexaenoic acids/d), whereas 251 patients comprised the control group. No group differences in the intake of energy and nutrients, apart from n-3 fatty acids, were discerned from dietary records. Compliance was affirmed by analyses of serum phospholipid fatty acids. Serum triglyceride concentrations were lowered by 19.1% in the fish-oil group, but no influence on the concentrations of cholesterol or apolipoproteins A-I and B-100 was seen. The concentrations of plasma glucose and serum insulin and C-peptide were not influenced by fish oil. The activity of liver enzymes increased slightly, but significantly, in the fish-oil group, whereas no group difference in the serum concentrations of thiobarbituric acid-reactive substances was observed. Thus, no adverse metabolic effects of long-term fish-oil supplementation assumed to be of clinical importance were seen.