Collagen metabolism was compared after anastomosis in the small and large intestine of rats. Animals were sacrificed 2 and 4 days postoperatively, when three standardized biopsy specimens were taken on either side of the anastomosis. In one group of rats, anastomosis was performed in both ileum and colon and 3H L-proline was given 24 hours before sacrifice, for studies of collagen synthesis. Animal weight, specimen dry weight, collagen concentration, collagen content per standardized biopsy, specific activity of collagen and total radioactivity were measured. Weight loss was greater after colon than after ileum anastomosis, indicating that the rats were more severely affected by colon surgery than by comparable operations on the ileum. Collagen content increased earlier and more in large intestinal than in small intestinal wall. The earlier activation of collagen synthesis in colon may have been related to differences in intestinal contents (e.g. bulk or bacteria).