Spiral coil membrane oxygenators made from either standard silicone rubber or silica-free silicone rubber were compared using three priming techniques. Standard priming, carbon dioxide priming, and denucleation priming were employed with each type of device. Four-hour venovenous membrane oxygenator perfusions were carried out on awake sheep anticoagulated with heparin. Virtually no differences were observed in any parameters measured between standard silicone rubber and filler-free silicone rubber membranes. Significantly greater platelet losses occurred during the first hour of perfusion with standard priming and with carbon dioxide priming than with denucleation priming, using either type of membrane. These experiments demonstrate that denucleation priming reduces platelet losses during extracorporeal membrane oxygenator perfusion, but that the use of filler-free silicone rubber does not improve the biocompatibility of the membrane.