The effects of recombinant human erythropoietin (rhEPO) on red blood cell (RBC) rheological properties were investigated in rats. Rats received intramuscular injections of 150 U/kg/d rhEPO for 5 d, following which blood samples were obtained 1, 5 or 10 d later. RBC deformability was assessed by determining cell transit times through 5-microm micropores (CTA) and RBC shape recovery time constants via photometry, aggregation in plasma and dextran was measured by photometry and RBC electrophoretic mobility was determined in a cylindrical electrophoresis system. RBC aggregation was found to be significantly decreased on day 5 after rhEPO treatment (P < 0.05), yet was unchanged from control on days 1 and 10. Mean RBC micropore transit times remained unchanged, but the distributions of transit times were altered; compared with control, the 5th percentiles on both days 1 and 5 were decreased and the 95th percentile on day 1 was elevated. Electrophoretic mobility of RBCs in phosphate-buffered saline was significantly increased on day 5 after rhEPO treatment (P < 0.05), with mobility measurements in dextran 500 (MW = 500 kDa) solutions suggesting that the cells' surface properties related to the formation of a 'depletion layer' may be altered on day 1. These results indicate that the rheological behaviour of RBC as a consequence of rhEPO treatment are temporal and are affected by the presence of reticulocytes as well as by the average age of the circulating cells.