The no-reflow phenomenon was studied following reconstitution of blood flow by microvascular anastomosis in an ischemic and denervated free epigastric flap in the rabbit. Microscopic, histological, angiographic, and hematological studies demonstrated the progressive nature of this obstruction to the peripheral blood flow after increasing periods of ischemia. This obstruction reached a point of irreversibility after 12 hours of ischemia, leading to ultimate death of these flaps. These results are consistent with the hypothesis that an ischemia-induced no-reflow phenomenon is caused by cellular swelling, intravascular aggregation, and the leakage of intravascular fluid into the interstitial space. Similarities between these experimental findings and human observations are made. The clinical importance of early diagnosis and treatment of ischemic tissues is emphasized.