Hepatic extraction of verapamil was determined directly in cardiac patients undergoing diagnostic catheterization and receiving 10 mg verapamil intravenously or intra-arterially. The extraction curves of verapamil concentrations in blood from the ascending aorta and hepatic vein were similar to those reported after single intravenous doses of indocyanine green. The rectilinear fall in concentration lasted 10 to 15 min. Mean hepatic extraction of verapamil in four patients who received intravenous doses was 0.86 (range 0.84 to 0.89) and in four who received intra-arterial doses was 0.87 (range 0.83 to 0.89). These estimates are the same as those for hepatic first-pass extraction determined by indirect methods based on areas under plasma concentration-time curves and requiring calculation of apparent hepatic blood flow. The results were considered to be proof that the first-pass effect of verapamil after oral doses is attributable mainly, if not entirely, to hepatic elimination.