Responses of blood platelets to bacterial endotoxin lipopolysaccharide (LPS) have been correlated with changes in the molecular organization and composition of the platelet plasma membrane proteins. Binding of LPS, which occurred in the absence of Ca2+, was distinguished from platelet aggregation and degranulation, which required Ca2+ and plasma proteins. Changes in membrane organization were detected by double-labelling with [125I] and [131I] iodide, mediated by lactoperoxidase and hydrogen peroxide. Changes in total membrane composition were detected by gel electrophoresis of isolated membranes. Binding of LPS was associated with increased accessibility of a protein of mol. wt. 80000 to iodination. After aggregation and degranulation there was, in addition, increased accessibility of proteins of mol. wt. 68000 and 48000. Isolated membranes from LPS-stimulated platelets contained more of a protein of mol. wt. 200000 and less of a protein of mol. wt. 220000 than control membranes prepared from unstimulated platelets in the presence of cAMP and aminophylline. The relationship of the modified plasma membrane proteins to the contractile proteins of the platelet and their possible redistribution in the cell during aggregation and secretion is discussed.