Very-low-calorie, fat-free defined-formula diets have been routinely used to treat obese patients. However, the effect of feeding a defined-formula diet low or devoid of essential fatty acids (EFAs) on EFA metabolism has not been determined. The aim of this investigation was to determine the effect of 400 kcal/day of Optifast 70 on EFA metabolism as determined by serum and adipose tissue levels of omega-6 fatty acids and measurements of in vitro human adipose tissue prostaglandin production. Five obese subjects entered the study after 1 wk of weight maintenance and then were placed on 12 wk of weight reduction. Blood and tissue samples were obtained before and after 4, 8, and 12 wk of weight reduction. Subjects tolerated 12 wk of dieting without any adverse reactions and lost an average of 21.7 +/- 7.0 kg. There was no significant effect of weight reduction on the levels of linoleic or arachidonic acid found in adipose tissue. There was a significant decrease in adipose tissue prostaglandin production of prostacyclin I2, measured as 6-keto-PGF1 alpha, after 12 wk of weight reduction. There was no significant change in the levels of thromboxane A2, measured as TXB2. There was a significant increase in serum arachidonic acid levels with no change in linoleic acid levels. The results demonstrated that the use of a diet devoid of EFA had no significant effect on omega-6 EFA metabolism as measured by serum and tissue levels and the ability of adipose tissue to produce prostaglandins in vitro.