ABSTRACT: Vanadium is an environmental pollutant attached to the smallest air suspended particles that enters into the respiratory tract reaching the systemic circulation. The oxidative state of this element and sex are factors related to its toxicity. In this study, we explored sex-associated genotoxic and cytotoxic differences in a mouse experimental model. Mice inhaled V2O5 (0.02 M) 2 h/twice a week; blood samples were obtained at 24 h and every week until the end of the 4-week exposure. Samples were processed for fluorochrome-mediated viability and a micronucleus assay in slides pre-covered with acridine orange (AO). The results showed that males were more susceptible to genotoxicity during the exposure in contrast to the females. In peripheral blood leukocytes, no cytotoxic differences were observed in both, females or males, but the decrease in circulating reticulocytes provides evidence of the metal's cytotoxic effect on the bone marrow (BM). A significant decrease in reticulocytes was observed during the experiment independent of the animal's sex. The present findings might be explained by the interaction of the metal with the enzymes that control erythropoiesis or a direct effect on erythropoietin production might explain our findings; however, an absence of the genotoxic effects in females could be a consequence of the protective effect against oxidative stress by their higher estrogen levels. This study contributes to a better understanding of the mechanisms by which vanadium induces adverse effects in biological systems. Copyright © 2013 John Wiley & Sons, Ltd.