Interaction between epidermal growth factor (EGF) and gastrin on DNA synthesis of the rat gastrointestinal tract was examined. Fasted male rats were divided into four groups and injected with 10 μg/kg human EGF, 300 μg/kg pentagastrin, human EGF plus pentagastrin and saline (control), respectively. The animals were sacrificed 8 or 16 hr thereafter and the incorporation of [3H]thymidine into the gastrointestinal mucosa was measured. Human EGF increased DNA synthesis of the fundus, antrum and cecum, while pentagastrin stimulated that of the fundus, duodenum, ileum and proximal colon. Synchronous administration of these peptides also stimulated DNA synthesis of the fundus, antrum and cecum. However, in the ileum and proximal colon, DNA synthesis stimulated by pentagastrin was suppressed by the administration of both agents synchronously. These data suggest that these growth factors regulate the growth of gastrointestinal tract with complex interactions.