AbstractWe investigated whether uptake of lactate anions by red blood cells (RBC) during maximal exercise altered certain cellular physical properties including volume, density and osmotic fragility. Irrespective of whether individuals undertook 1min of exercise at maximal effort or a progressive exercise test to exhaustion, whole-blood lactate concentration increased about tenfold relative to pre-exercise values (P0.001). The plasma and cellular concentrations of lactate increased uniformly, which maintained a constant plasma-to-cell gradient. Exercise-induced increases in RBC osmotic fragility (P0.001) and mean cell volume (MCV;P0.05), and decreases in mean cell haemoglobin concentration (MCHC;P0.05) and cell density (P0.005) also occurred. These exercise-induced cellular responses could be simulated in vitro by treating blood with L-lactic acid (15mm), but not by low pH (7.1) or L-lactate alone. The uptake of lactate by RBCs during vigorous exercise alters certain cellular properties. Although the physiological implications of these changes are unclear, the traditional view that the lactate anion has no known harmful effects should be reconsidered.