Sixty marrow transplant recipients with liver dysfunction underwent transvenous liver biopsy and measurement of the hepatic venous pressure gradient. Biopsies were done on 29 patients using a Cook needle inserted through the jugular vein, on 30 patients through the femoral vein with a Mansfield biopsy forceps, and on 1 patient using both instruments. The average number of evaluable portal spaces was 4.0 for aggregated Cook needle specimens and 5.2 for Mansfield forceps specimens. The average number of central venules was 2.6 for Cook needle specimens and 3.5 for Mansfield specimens. Tissue obtained with the Mansfield forceps had crush artifact, especially along the edges, making assessment of bile ducts more difficult than in Cook needle specimens. Liver histology aided management in 53/60 patients by confirming the clinical diagnosis in 24 (40%) and by providing additional diagnoses in 29 (48%). Hepatic venous pressure gradient > 10 mmHg correlated with a histologic diagnosis of veno-occlusive disease (P = 0.001); this gradient value provided 91% specificity and 86% positive predictive value. Eleven patients had bleeding complications, 9 after Cook needle biopsy and 2 after Mansfield forceps biopsy. There were 3 procedure-related deaths, 2 from intraperitoneal bleeding after Cook needle biopsy and 1 from femoral vein bleeding after Mansfield biopsy. We conclude that transvenous liver biopsy and pressure measurements provide useful diagnostic information in marrow transplant patients with liver disease. In our hands, the Mansfield forceps was associated with a lower risk of intra-abdominal bleeding and capsular perforation of the liver while providing adequate histology for diagnosis. Hepatic venous pressure gradients > 10 mmHg were highly specific for a diagnosis of veno-occlusive disease in this patient population.