Atrial natriuretic peptide (ANP) increases renal sodium and water excretion in several species including man. In rats ANP was also found to influence water and electrolyte transport in the small intestine. In the present study we investigated whether ANP can alter transport in the jejunum and ileum of healthy volunteers using a triple-lumen perfusion technique. The small intestine was perfused under steady-state conditions with a plasma-like electrolyte solution using polyethylene glycol as a nonabsorbable volume marker. After an initial control period with intravenous saline infusion ANP was administered intravenously at a dose of 400 pmol kg-1 h-1. This dose led to a significant (P less than 0.05) increase in the plasma levels of ANP (up to 22-fold) and cGMP (up to 15-fold), and of urine volume. Intestinal water and electrolyte transport were, however, not affected by ANP. Our results suggest that circulating ANP does not play a role in the regulation of mucosal water and ion transport in the human small intestine.