Background: Liver disease associated with cystic fibrosis may not only limit the solubilisation and absorption of the products of fat digestion, but also may depress the activity of pancreatic Lipase. The purpose of this study was to measure the effect of Liver disease on triacylglycerol Lipolysis using the C-13-mixed triacylglycerol breath test. Methods: Forty children with cystic fibrosis took C-13-mixed triacylglycerol with a standard breakfast and the child's normal pancreatic enzyme replacement therapy. Breath samples were collected before and every 30 minutes after ingestion for 6 hours. The cumulative percentage dose of C-13 recovered at 6 hours was calculated from sequential measurements of C-13 enrichment of breath CO2, measured by isotope ratio mass spectrometry. Liver abnormalities and portal hypertension were defined by ultrasound scan and clinical examination. Results: Twenty-four children had liver abnormalities, including 5 with portal hypertension. No difference was found between cumulative percentage dose of C-13 recovered at 6 hours in 16 children with no liver abnormality (mean, 21.4% +/- 11.1%), 19 children with liver abnormalities (22.2% +/- 10.0%) and 5 children with portal hypertension (20.9% +/- 7.1%). Conclusion: Intestinal lipolysis is not reduced in cystic fibrosis Liver disease when measured using the C-13 mixed triacylglycerol breath test. These findings affirm the test's use as an indirect measure of fat digestion that is not affected by inadequate intraluminal bile salts or liver disease.