The concept of the partial Fontan procedure, first described with the adjustable atrial septal defect (ASD) and more recently with the fenestrated technique, has become an accepted approach for the management of high-risk patients undergoing the Fontan procedure. Experience with both techniques has shown that a patent ASD placed in a prosthetic interatrial baffle may close spontaneously over a period of weeks to months. The mechanism and timing of spontaneous closure, as well as the effect of antiplatelet therapy on this process, are poorly understood. To better define this process, the interatrial septum of 15 mongrel dogs was excised and replaced with a fenestrated Gore-Tex (W.L. Gore, Flagstaff, AZ) patch. Postoperative echocardiography confirmed the patency of the ASD and left-to-right shunting. Animals were sacrificed 4 to 6 weeks postoperatively, or sooner if infection or other postoperative complications developed. Eight animals underwent no antiplatelet or anticoagulation therapy postoperatively, and 7 received antiplatelet therapy with aspirin. Patches were removed at the end of the study period and analyzed. By 6 weeks, all 2.7-mm and 4-mm holes had closed spontaneously in all animals that had not received antiplatelet therapy. The earliest closure occurred at 1 week. With antiplatelet therapy, hole closure was found to be delayed but not prevented, and was complete by 6 weeks in all but 1 animal. Histologic examination of the explanted patches revealed that closure was accomplished primarily through the ingrowth of fibrous tissue, accompanied by an inflammatory cell infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS)