To identify evidence of essential fatty acid deficiency, we screened 64 patients with cystic fibrosis by analyzing total lipid extracts from plasma. Forty-three had an abnormal linoleate (18:2) level (less than 26%). Thirteen deficient patients (aged 10-24 yr) ingested for 1 yr 7% of their total calories as linoleate derived from a daily supplement of Microlipid. Five deficient patients (aged 10-37 yr) served as controls. Plasma and erythrocyte fatty acid composition were monitored by gas chromatography of total lipid extracts seven times during the twelve month period. Prostaglandins E2and F2αand their 15 keto 13, 14 dihydrometabolite, 6-keto F1α, and thromboxane B2were measured by radioimmunoassay. Sweat tests, oxygen saturation, growth indices, clinical severity scores, compliance, and possible side effects from taking Microlipid were followed. Results showed that oral supplementation with Microlipid can significantly increase plasma and erythrocytes %18:2. One compliant patient died during the study and had normal tissue 18:2 levels. Nine of 13 patients gained more weight while taking Microlipid than in the previous year. No significant changes in sweat electrolytes, clinical scores, or oxygen saturation were found during the study year. Prostaglandin metabolites prostaglandin E2showed an upward trend in supplemented patients, compared to controls. Prostaglandin F2αremained unchanged over 1 yr but showed a trend significantly downward over the final 6 months in supplemented patients. We conclude that linoleate deficiency can be corrected with daily Microlipid supplements and that correction may alter prostaglandin metabolism