The possibility that the central and autonomic nervous systems might be involved in the control of intestinal absorption was assessed by measuring the effect of physical stress (cold-induced pain) on jejunal transport in 13 healthy subjects. Using a triple-lumen perfusion technique to determine jejunal absorption, cold pain significantly reduced net water absorption from 34.9 to 15.7 ml/30 cm.50 min (p less than 0.005), net sodium absorption from 2.6 to 0.2 mEq/30 cm.50 min (p less than 0.005), and net chloride absorption from 2.2 to 0.6 mEq/30 cm.50 min (p less than 0.02). These changes were associated with an elevation of blood pressure and plasma norepinephrine during cold pain. During the period following cold pain, systolic blood pressure remained significantly elevated and net jejunal water absorption significantly reduced. These results suggest that physical stress can influence jejunal absorption of salt and water in humans and support the possibility that the central and autonomic nervous systems have a physiologic role in the control of intestinal function.