To evaluate how creatine influences erythrocyte deformability, we determined its effect on erythrocyte filterability in 9 subjects with insulin dependent diabetes (IDDM) without complications, 14 diabetics with uremia and 10 non-diabetic controls. The short-term incubation (15 min at 37 degrees C) of diabetic erythrocytes with 3 mM creatine improved cell filterability (assessed according to the Reid method) from IDDM subjects without complications by 28.4% and that from diabetics with uremia by 18.9%. No rheological effect of creatine was found in erythrocytes from non-diabetic controls. However, a significant protective effect against erythrocyte filterability impairment induced by treatment of red blood cells from non-diabetic controls with hydrogen peroxide was observed with 3 mM (p < 0.04) and 5 mM (p < 0.01) creatine, respectively. Measurement of the thiobarbituric acid (TBA) reactivity was used to assess hydrogen peroxide induced formation of malondialdehyde (MDA). We found that creatine inhibits hydrogen peroxide-induced erythrocyte MDA-formation in a dose dependent manner by 20.4%, 22.3% and 41.4% for 1, 3 and 5 mM creatine, respectively. These results suggest that creatine by its ability to inhibit erythrocyte lipid peroxidation may contribute to the maintenance of normal cell deformability.