Abstract Platelet membrane glycoprotein lb (GPlb) in stored platelet concentrates was analyzed by flow cytometry with three separate monocional antibodies (AN-51, 6D1, and SZ-2), by tritiated glycoprotein a radiolabeling, and by ristocetin-induced agglutination. Flow cytometry showed that a population of surface GPlb-negative platelets was evident at 5 days and increased three- to fivefold by the tenth day. Tritium radiolabeling of surface GPlb showed a decrease over 10 days of 37% ± 17%.The degree of loss of surface GPlb correlated well with other changes during storage: decreased ristocetin-induced agglutination, decreased responsiveness in the hypotonic shock test, lower plasma pH, and increased extracellular lactic dehydrogenose. Immunoblotting of total platelet GPlb with the SZ-2 antibody showed a decrease of 58% ± 16% during the 10-day storage period. The effect of protease inhibitors or platelet activation inhibitors on the loss of GPlb during storage was studied in platelet concentrates paired with untreated control. Only the platelet activation inhibitors prostaglandin E 1 and theophylline retarded the loss of surface GPlb levels (93% ± 5% GPlb remaining vs 65% ± 16%). Total GPlb levels also decreased less in the presence of the activation inhibitors (45% ± 22% lost vs 70% ± 14% lost). These findings suggest that platelet activation, rather than plasma enzymatic activity, is responsible for the loss of platelet GPlb during storage of platelet concentrates.