The liver plays a central role in the metabolism of polyunsaturated fatty acids. We studied the relationship between essential fatty acid (EFA) status and indicators of liver function in 15 children with chronic cholestasis aged 9 months to 3.4 years (median, 1.3 years). Compared with 13 control children, the patients studied had low percentage values of phospholipid EFAs, particularly of the omega-6 fatty acids linoleic acid (18:2omega-6) and arachidonic acid (20:4omega-6). Fatty acid values exhibited an inverse relationship to serum bile acids, as well as to serum bilirubin. Bilirubin values were unrelated to the EFA precursors linoleic acid and alpha-linolenic acid but correlated inversely with the long-chain metabolites arachidonic acid (r = -0.75; p = 0.001), docosapentaenoic acid (22:5omega-3; r = -0.63; p = 0.01), and docosahexaenoic acid (22:6omega-3; r = 0.72; p = 0.002). We conclude that children with chronic cholestasis are at a high risk for EFA deficiency, which increases with progressive elevation of serum bilirubin. Hepatic conversion of essential precursor fatty acids into their long-chain metabolites may be increasingly impaired with advancing severity of liver disease.