We have studied the fatty acid composition of erythrocyte membrane phospholipids in nine Type 1 (insulin-dependent) diabetic patients and nine healthy control subjects. Cell membranes from the diabetic patients showed a marked decrease in the total amount of polyunsaturated fatty acids (19.0% +/- 2.2 vs 24.6% +/- 1.4, p < 0.0001) mainly at the expense of docosahexaenoic acid C22:6(n3) (2.9% +/- 1.1 vs 5.3% +/- 1.3, p < 0.001), and arachidonic acid C20:4n6 (12.0% +/- 1.6 vs 15.1% +/- 0.6, p < 0.0005). Conversely, the total amount of saturated fatty acids was significantly increased (p < 0.05) and the polyunsaturated/saturated ratio was decreased in the Type 1 diabetic patients (p < 0.00 005). Neither the time from diagnosis, nor C-peptide levels, correlated with parameters indicating a poor metabolic control of Type 1 diabetes. However, C22:6(n-3) and total n-3 content significantly correlated with HbA1c (r = -0.79 and r = -0.88, respectively, p < 0.01), fructosamine (r = -0.71 and r = -0.74, respectively, p < 0.05), and Na+-K+ ATPase activity (maximal rate/Km quotient) (r = 0.78 and r = 0.71, respectively, p < 0.05). In conclusion we have found marked alterations of cell membrane lipid composition in Type 1 diabetic patients. These cell membrane abnormalities in lipid content were related to sodium transport systems and to poor metabolic control. Either diet, or the diabetic state, might be responsible for the observed cell membrane abnormalities. A dietary intervention study might differentiate the role of diet and diabetes in the reported cell membrane alterations.