Deformability of red blood cells and the lipid composition of their plasma membranes were studied in ten long-distance runners, in comparison with ten sedentary matched controls. Mean corpuscular volume and corpuscular hemoglobin concentration did not differ between these groups, while the hemoglobin concentration and hematocrit were lower in the former. Deformability was measured in terms of the erythrocyte suspension filterability through 5 microm microchannels, using an array flow analyzer, and was significantly elevated in athletes. Analysis of the membrane phospholipid composition of red blood cells revealed an increased ratio of phosphatidylcholine to phosphatidylethanolamine and a decreased ratio of cholesterol to total phospholipids in athletes. The length and saturation levels of fatty acid acyl chains were unchanged. Multiple regression analysis showed clearly that these alterations of membrane lipids correlate with increased deformability and thus favor circulation in the microvasculature in long-distance runners.