Erythrocytes were incubated for 60 min either in plasma or phosphate-buffered saline containing 10 mM phenylhydrazine hydrochloride. Plasma prevented the decrease in membrane fluidity observed in saline-phenylhydrazine incubated erythrocytes but these cells showed decreases in both filterability and active extrusion of Na+ that were nearly 100% lower than those found in erythrocytes incubated in plasma-phenyl-hydrazine. Also erythrocyte lipid peroxidation, as measured as thiobarbituric acid reactive products, was 100% higher in the presence of plasma. These results suggest that plasma could play "in vivo" an active role during oxidant-induced erythrocyte damage, contributing significantly to the hemolytic effects of oxidation.