During prolonged fasting in lizard and rat, plasma levels of unesterified cholesterol (UC) and phospholipids (TPL) decreased and there were reductions and increases, respectively, in the molar ratios of lecithin (PC) to sphingomyelin (SPH) and UC to TPL. Plasma lecithin: cholesterol acyltransferase (LCATase) activity in lizard and rat plasma was reduced during prolonged fasting. Erythrocyte lipid composition for fasted animals was also characterized by a reduction in the molar ratio PC/SPH and an increase in UC/TPL, and in both species there were positive correlations between these molar ratios in red cells and those in plasma. In both species these were changes in the morphology of the erythrocytes, and those from fasted rats showed alterations in osmotic fragility and permeability which correlated with alterations in lipid composition. These results suggest that changes in plasma lipoprotein lipid composition, linked to reduced LCATase activity, may cause similar alterations in the lipid composition of red cell membranes leading to altered membrane properties.