Recombinant human erythropoietin (EPO), commercially available since 1988, is thought to be used by athletes in aerobic sports for the purpose of increasing oxygen transport and aerobic power. In an attempt to identify EPO administration, we have studied the peripheral blood of 20 subjects practising sports at an amateur level. Automated cytometry was performed on the blood samples before and during 45 days of EPO treatment. The same hematological indices were determined for a control population that consisted of 240 elite athletes from various sports. As expected following EPO treatment, RBC, [Hb] and Hct increased significantly (increments of 8%, 6.3% and 11%, respectively). A significant increase in reticulocyte count was also observed. In addition, automated erythrocyte analysis showed a significant increase in cells with a volume > 120 fl and hemoglobin content (HC) < 28 pg (hypochromic macrocytes, or MacroHypo): 0.06 +/- 0.09% before EPO, 0.48 +/- 0.63% after EPO. The EPO-treated subjects differed from the control population having higher values for Hct, mean corpuscular volume (MCV), Macro and MacroHypo. To investigate the possibility of using such variations in blood parameters to identify EPO treatment, individual values for Hct, MCV, Macro and MacroHypo for treated subjects and controls were plotted. Using the percentages of MacroHypo, a cut-off value surpassed in approximately 50% of the treated subjects and in none of the controls was established.(ABSTRACT TRUNCATED AT 250 WORDS)