Five undernourished children with severe cerebral palsy (CP) were tube-fed sufficient volumes of Isocal to allow rapid weight gain. Isocal provided, on average, 88% of their daily energy intake for at least 25 days. The purpose of our study was to correct the undernutrition and to analyze the major erythrocyte phospholipids before and after feeding periods for possible feeding and disease-related differences. The fatty acid profiles of erythrocyte membranes from CP children were compared with those from 12 healthy children and with the fatty acid composition of the formula. There were no clinical or biochemical indications of essential fatty acid deficiency. The feeding of a soy oil-based formula increased the proportions of 18:2n-6 in the phospholipids. The increases occurred predominantly in phosphatidylcholine followed by phosphatidylethanolamine. Despite such large dietary intakes of soy oil, no changes were observed in the phospholipid concentrations of 20:4n-6, 18:3n-3, 20:5n-3, or in the C22n-6 and C22n-3 fatty acids. These findings are consistent with an inhibition of the delta 6 desaturase by high dietary linoleate.