The fatty acid composition of plasma and erythrocyte phospholipids was determined in children with various subtypes of epidermolysis bullosa (EB) and in their parents. Patients with recessive dystrophic, dominant dystrophic, simplex, or junctional forms of EB had a higher percentage composition of arachidonic acid in plasma and/or erythrocyte phospholipids compared to age-matched controls. Epidermolysis bullosa patients treated with diphenylhydantoin had lower levels of arachidonic acid in plasma and erythrocyte phospholipids than did untreated EB patients. Parents of children with the recessive dystrophic or junctional EB subtypes had higher linoleic and arachidonic acids in plasma and erythrocyte phospholipids than did controls. Plasma and erythrocyte total lipids were within the normal range in children with EB. Plasma zinc was also normal but plasma copper was elevated in children with recessive dystrophic EB. We conclude that higher arachidonic acid in plasma and erythrocytes may be related to the pathology of EB.