Sixteen healthy females were randomly assigned to receive fish oil or corn oil double blind in a 28 days intervention period. Osmotic fragility of erythrocytes was decreased in the fish-oil supplemented group and not affected in the corn-oil group. The decrease in osmotic fragility was maximal after 14 days and approached the pre-intervention level after 24 and 28 days of n-3 supplementation. No change was observed in erythrocyte membrane fluidity in either of the groups. The level of n-3 fatty acids increased significantly in erythrocytes from the fish oil supplemented subjects, mainly at the expense of linoleic acid (18:2, n-6) and oleic acid (18:1). No significant change was seen in the relative amount of arachidonic acid (20:4,n-6) or in the phospholipid/cholesterol ratio in erythrocytes, while the ratio between the sum of phoshatidylcholine and sphingomyeline/phosphatidylethanolamine (PC+SM/PE) increased during the intervention period. This study does not verify the hypothesis of a relationship between osmotic fragility and membrane fluidity. It is concluded that increased level of n-3 fatty acids in erythrocyte membranes decreases osmotic fragility, and that this effect is counteracted by increased PC+SM/PE ratio.