BACKGROUND: Erythropoiesis is partly regulated through classic feedback pathways that govern blood volume (BV) as sensed by veno-atrial but also arterial stretch receptors. Hence, the total volume of red blood cells (RBCV) could be associated with arterial stiffness (AS), although such hypothesis has not yet been tested. Therefore, we sought to investigate the association of AS with hematological variables including RBCV. METHODS: Fourteen healthy physically active individuals volunteered for the study (age=23±2). RBCV, plasma volume (PV), and BV were calculated from measures of hematocrit and total hemoglobin mass (Hbmass) determined by CO-rebreathing. Carotid compliance with ultrasonography and carotid-ankle pulse wave velocity (PWV) were determined at rest and immediately after a maximal exercise test. The rationale for assessment of AS after exercise derives from the potential marked role of AS in the regulation of erythropoiesis in the setting of reduced central venous pressure. RESULTS: At rest, carotid compliance was positively associated with Hbmass, RBCV, BV, but not PV, with coefficients of determination (R(2)) ranging from 0.39 to 0.57. Following exercise, closer positive associations were observed between carotid compliance and Hbmass, RBCV, or BV. Moreover, carotid-ankle PWV was negatively associated with all hematological variables after exercise except for PV, with R(2) ranging from 0.49 to 0.75. Similar results were observed when adjusted by body weight. CONCLUSIONS: AS is strongly and inversely associated with RBCV in healthy individuals. These findings suggest that AS may adversely intercede in the regulation of erythropoiesis through the alteration of mechanisms that control BV.