The relative concentration of fatty acids in plasma and platelet phospholipids (phosphatidylcholine) was determined in 11 patients with overt hypothyroidism (S-TSH>80 mU/l) before and after l-thyroxine substitution therapy. During therapy, the linoleic (C18:2) acid content decreased (p<0.01) whereas longer and more desaturated fatty acids, including arachidonic (C20:4) acid, increased (p<0.01) in plasma phospholipids. Also, oleic (C18:1) acid decreased (p<0.01) while the major saturated fatty acids, palmitic (C16:0) and stearic (C18:0) acids, were stable. In platelet membrane phospholipids, a similar reciprocal change in the relative content of linoleic (C18:2) and arachidonic (C20:4) acids, respectively, occurred. In plasma, these changes in linoleic and arachidonic acids were found to be inversely correlated (r=0.56, p<0.05). The change in the linoleic acid content in plasma was also correlated to that in platelets (r=0.64, p<0.05). Thus, we have found that thyroid hormones positively influence the conversion of linoleic acid to longer and more polyunsaturated fatty acids in a way that affects fatty acid composition not only in plasma but also in platelet membrane phospholipids.