The metabolism of apoprotein B-containing plasma lipoproteins by human splanchnic tissues has been studied in 29 men undergoing coronary angiography. Before catheterization autologous radio-iodinated lipoproteins were infused into a peripheral vein: 10 subjects received (125)I-labeled Sf 12-60 lipoproteins; 12 received (125)I-labeled Sf 12-60 plus (131)I-labeled Sf 100-400 lipoproteins; and 7 received (125)I-labeled Sf 12-60 plus (131)I-labeled Sf 0-12 lipoproteins. Paired arterial and hepatic vein blood samples were subsequently collected for replicate measurements of apoprotein B (apo B) mass, radioactivity and specific activity in each lipoprotein class. Splanchnic plasma flow was measured with indocyanine green. All studies were conducted after a 14-h overnight fast. Newly synthesized apo B was shown to be secreted by splanchnic tissues as a component of Sf 100-400 lipoproteins, with no detectable uptake of apo B from this class. Sf 12-60 apo B was extracted by the splanchnic bed, with no detectable secretion. After continuous intravenous infusion of (125)I-labeled Sf 12-60 for five or more hours, 41-67% (mean 55%) of extracted Sf 12-60 apo B radioactivity reappeared in hepatic vein Sf 0-12 apo B. There was no detectable splanchnic catabolism of Sf 0-12 apo B. The rates of Sf 100-400 apo B secretion, calculated as the product of artery-hepatic vein concentration difference and splanchnic plasma flow, were greater than the previously reported rates of very low density lipoprotein apo B turnover in fed subjects obtained by kinetic analysis of plasma specific radioactivity decay curves, suggesting that there may be a diurnal variation in hepatic apo B synthesis. They also exceeded the splanchnic extraction rates of Sf 12-60 apo B, suggesting there was some extrasplanchnic catabolism of the apo B of Sf > 60 lipoproteins.