Essential fatty acid deficiency (EFAD) occurs in infants fed fat-free mixtures of glucose and amino acids. Although infusion of lipid emulsion rapidly reverses clinical symptoms, little is known about effects on tissue fatty acids. To study this question, five groups (n=4/ group) of neonatal pigs were studied. Three groups (I, II, and V) were made EFAD by feeding diets without essential fatty acids (EFA) for days 5 to 33 of life. Groups III and IV were fed a control diet. By 33 days, animals fed the deficient diet showed clinical symptoms and biochemical signs of EFAD. On days 33 to 54 of life, group I animals were fed the EFA-deficient diet and infused with lipid emulsion, providing 3.6% of energy as linoleic acid; group II animals were fed the deficient diet and infused with linoleic acid at 7.2% of energy; group V animals were fed the deficient diet with no lipid emulsion; group III and IV animals were fed the EFA-deficient diet and provided EFA intravenously. Infusion of lipid emulsion rapidly reversed clinical symptoms of EFAD and returned plasma phospholipidω6 fatty acids levels to normal. However, erythrocyte and liver phospholipidω6 fatty acid content and adipose tissue reserves ofω6 fatty acids normalized more slowly. Three weeks of infusion of linoleic acid at 3.6% of energy and 2 weeks of infusion at 7.2% of energy were required to return erythrocyte phospholipid fatty acids to normal. Liver phospholipid fatty acid composition still showed biochemical evidence of EFAD in animals treated with linoleic acid at 3.6% of energy for 3 wk. Adipose tissue reserves ofω6 fatty acids did not return to normal in animals treated for 3 wk with linoleic acid at 3.6% of energy. Two to 3 wk of treatment with linoleic acid at 7.2% of energy was required to return adipose tissue 6ωfatty acids reserves to normal.