In order to assess the effect of food ingestion on splanchnic disposal of human alpha-atrial natriuretic peptide (ANF), hepatic-intestinal removal of ANF was determined before and after a test meal. Hepatic venous and arterial plasma samples were obtained from six subjects, most of whom had only disorders of minor degree. Hepatic blood flow (HBF) increased significantly after meal ingestion (1.10 ± 0.17 [SEM] to 1.51 ± 0.26 L/min, P < .01). Baseline arterial ANF (10.9 ± 3.1 pmol/L) did not change significantly. In contrast, hepatic venous ANF increased after meal intake (5.7 ± 2.0 to 8.4 ± 1.9 pmol/L, P < .05), and accordingly the splanchnic fractional extraction decreased (0.53 ± 0.09 to 0.35 ± 0.08), although this was not statistically significant. Splanchnic clearance of ANF increased from 347 ± 90 mL/min to a maximal value of 615 ± 158 mL/min (P < .05). Splanchnic removal of ANF was 3.0 ± 0.5 pmol/min before and increased to a maximum value (7.1 ± 2.2 pmol/min, P < .05) 35 minutes after ingestion of the meal. Our results showed enhanced splanchnic removal of ANF after food intake. This is due to increased hepatic-intestinal clearance of the peptide consequent on increased splanchnic blood flow, rather than altered fractional extraction of ANF.