In anesthetized dogs, the effects of a gentle manipulation of the gut wall, increasing the lumen pressure to 20 mmHg by distention, or an intravenous infusion of physostigmine on blood flow distribution within the wall of the gastrointestinal tract were studied with radioactive microspheres. Manipulation and distension produced rhythmic contractions and increased flow to the distended and manipulated segments. The increased flow was confined to the muscularis serosa; the mucosa-submucosa flow was unchanged. Physostigmine produced a sustained tonic contraction and decreased flow to the whole wall of the stomach, duodenum, jejunum, ileum, and colon. The decreased flow was confined to the mucosa-submucosa; the muscularis serosa flow was unchanged. Thus, the muscularis serosa vasculatures escape the effects of a fall in vascular transmural pressure during the tonic contraction. Manipulation, distention, and physostigmine all increase the percentage of total wall flow perfusing the muscularis serosa. These studies suggest that active hyperemia, similar to exercise hyperemia in skeletal muscles, occurs in the muscularis of gut wall during intestinal contractions.