The participation of mast cells in connective tissue repair was studied using the perforated-rat-mesentery model. Perforation of mesenteric membranes was performed during laparotomy of anesthetized Sprague-Dawley rats. Laparotomy significantly reduced the histamine content of the mesenteric membranes on day 1 postoperatively and perforation as such reduced the histamine content even more on days 1-10. Mast cell activation induced by a single intraperitoneal injection of Compound 48/80 two days prior to operation, significantly improved healing on days 5-7 postoperatively. Daily injections of Compound 48/80 for 5 days prior to operation showed significantly better healing compared to such injections for five days postoperatively. Administration of lupitidine, a long acting histamine H2-receptor antagonist, two times daily starting on the day of 48/80 injection to day 4 after operation did not apparently affect healing. The results indicate that mast cells may be activated during normal wound healing and that a preoperative, pharmacological activation improves healing. Furthermore, histamine does not seem to be of major importance for the beneficial effect of such mast cell activation on connective tissue repair.