Spiculated red blood cells (RBCs) (echinocytes) and decreased levels of plasma lipoproteins developed concomitantly in severely burned (more than 35% body surface burned) patients. The RBCs were characterized as flat cells with spicules evenly distributed over the surface, and the erythrocyte lipid content was slightly increased. No evidence of excessive hemolysis was found, although modest shortening of RBC life-span could not be excluded. Development of echinocytes presaged a poor prognosis similar to that observed with acanthocytosis in cirrhosis. Striking decreases in plasma α-lipoprotein, cholesterol, and phospholipid values were observed and could be explained in part by loss of α- and pre-β-lipoproteins through damaged microvasculature as these were recovered from blister fluid. Decreased plasma lipoproteins and echinocyte development appeared to be temporally related; the degree of echinocytosis correlated with decreases in plasma lipid values and plasma protein values, but no causal relationship can be inferred because of the multiplicity of changes in severely burned patients. (<i>Arch Intern Med</i>136:71-76, 1976)