Assumed to rely on an axon reflex, the current-induced vasodilation (CIV) interferes with the microvascular response to iontophoretic drug delivery. Mechanisms resulting in CIV are likely different at the anode and at the cathode. While studies have been conducted to understand anodal CIV, little information is available on cathodal CIV. The present study investigates CIV observed following 0.1-mA cathodal applications on forearms of healthy volunteers, and the possible mechanisms involved. Results are expressed in percent of the cutaneous heat-induced maximal vascular conductance (%MVC [mean±SEM]). 1/ The amplitude of CIV was proportional to the duration of cathodal currents for period of less than 1-min: r=0.99. 2/ Two current applications of 10s, with 10-min inter-stimulation interval, induced a higher peak value of CIV (79.1±8.6%MVC) than the one obtained with all-at-once 20s current application (39.5±4.3%MVC, p<0.05). This amplified vascular response due to segmental application was observed for all tested interstimulation intervals (up to 40 min). 3/ Two hours and three days following pre-treatment with 1g oral aspirin, the CIV observed following cathodal application, as well as the difference of cathodal CIV amplitude between all-at-once and segmented applications were reduced. These findings suggest a role of prostaglandins, not only released from endothelial or smooth muscle cells, as direct vasodilator and/or as a sensitizer. Thus, aspirin pre-treatment could be used to decrease CIV resulting from all-at-once and repeated cathodal application and facilitate the study of the specific vascular effect induced by the drug delivered.