Acute cellular necrosis occurring minutes to hours after massive ionizing radiation exposure (IR) results from rapid membrane lipid peroxidation, blebbing and membrane breakdown. We have shown, previously, that certain polymer surfactants can restore structural integrity and transport barrier function of cell membranes following high-dose IR. We now investigate, specifically, the efficacy of the amphiphilic surfactant Poloxamer 188 (P188) in preventing acute necrosis of adult rat skeletal muscle cells after high-dose IR. Explanted cells were treated with 60Co IR doses of 10, 40 or 80Gy and their viability was determined using fluorometric probes at 4 and 18h post-IR. IR of 10Gy did not cause acute necrosis. Significant acute cell necrosis was observed after 40 and 80Gy doses in a dose-dependent manner. Post-IR treatment with P188 significantly enhanced the cells' viability post-IR treatment. By comparison 10kDa neutral dextran, a hydrophilic polymer, was found to be ineffective. Despite progressive cell death over 18h after high-dose IR, cells treated with P188 manifested greater survival than media or dextran-treated cells. It appears that use of P188 or similar multi-block copolymers to prolong viability of irradiated cells in vitro through membrane sealing is an important step in development of effective interventional therapy for extreme IR exposure. Not only can repairing the membrane prevent acute necrosis, but it also can provide a critical time opportunity to address other mechanisms of cell death, such as apoptosis or mitotic arrest, which manifest over a longer time frame.