During regional isolated perfusion, neoplasms in extremities are treated with high doses of chemotherapeutic drugs by means of an extracorporeal circuit. The question is whether optimal tissue perfusion, which is essential for the therapy, is obtained by regulation of the extracorporeal circuit on an adequate perfusion flow or on an adequate perfusion pressure. To determine which perfusion pressure is needed to maintain adequate tissue perfusion, hindlimbs of six dogs were perfused at perfusion pressures 0, 15, 25, and 50 mm Hg below systemic mean arterial pressure. A multiwire polarographic oxygen electrode placed on the sartorius muscle permitted quantitative evaluation of tissue oxygenation by means of ptO2 histograms. Our results indicated that the perfusion pressure must be equal to or within 15 mm Hg below systemic mean arterial pressure to obtain optimal tissue perfusion. To maintain this perfusion pressure, high perfusion flows of about five to 10 times control femoral flows were needed. At a perfusion pressure 50 mm Hg below systemic mean arterial pressure, perfusion flow was normal, but tissue perfusion was severely impaired.