The effect of obesity and jejunoileal bypass on the amount and composition of hepatic lipid and the relationship of adipose tissue fatty acids, body weight, and rate of weight reduction to hepatic triglyceride (TG) were investigated in 16 patients before and at various times after jejunoileal bypass. Liver and adipose tissue biopsy sections were taken at surgery and at various times thereafter. Hepatic lipid was measured and the composition of triglyceride fatty acids (TGFA) compared with that of adipose tissue. Liver TG increased by an average of 2.5-fold during the period of rapid weight loss and decreased during the period of stable weight, but remained above control values. There was no relationship between concentration of liver TG and body weight or rate of weight reduction. The hepatic TGFA composition at surgery and during the period of stable weight resembled that of adipose tissue. During the period of rapid weight loss the composition of hepatic TGFA was markedly different, showing an increase in palmitic (16:0, P less than 0.01), palmitoleic (16:1, P less than 0.05), and oleic acids (18:1, P less than 0.05) and a decrease in linoleic acid (18:2, P less than 0.001). These changes could not be accounted for by a preferential absorption or mobilization of 16:0, 16:1, and 18:1, or by an increased utilization of 18:2 by the liver. It is proposed that an increased conversion of carbohydrate to fat occurs during the period of rapid weight loss when a relative excess of carbohydrate to amino acids results from an imbalance in the intestinal absorption of carbohydrate and protein.