Temporary inhibition of platelet function with prostaglandin E1 (PGE1) prevents platelets loss and functional alterations during extracorporeal circulation with a membrane oxygenator. This study evaluated the ability of PGE1 to prevent platelet injury in circuits containing a bubble oxygenator. During in vitro recirculation of human blood, the circulating platelet count, expressed as a percent of initial levels, decreased to 29%; platelets became insensitive to adenosine diphosphate (ADP) and to epinephrine; and plasma levels of low-affinity platelet factor 4 (LA-PF4) progressively rose to 7.4 microgram per milliliter. With PGE1 (1.2 micron), platelet counts remained stable at 92%; platelet reactivity remained normal for 1 hour; and plasma levels of LA-PF4 rose to only 3.3 microgram per milliliter. In rhesus monkeys that underwent cardiopulmonary bypass using a bubble oxygenator without PGE1, platelet counts, expressed as a percent of the prebypass platelet count, declined to 38%; platelets became insensitive to ADP; plasma levels of LA-PF4 progressively rose to 8.4 microgram per milliliter; and the mean postoperative bleeding time was 4.6 minutes. In monkeys that received PGE1, platelet counts declined to only 65%; platelets remained threefold more sensitive to ADP; platelets demonstrated delayed release of LA-PF4 and the mean postoperative bleeding time was 2.7 minutes. This report demonstrates that in a bubble oxygenator system, PGE1 reduces platelet loss, mitigates platelet injury, and shortens postoperative bleeding times following extracorporeal circulation.