We used laser Doppler perfusion imaging (LDPI) to study nonspecific vasodilatation during iontophoresis. In iontophoresis studies, nonspecific vasodilatation occurs as a result either of galvanic currents or of the applied voltage over the skin. We made dose–response measurements to study the effect of ionic strength of the vehicle on the nonspecific vasodilatation during iontophoresis of sodium chloride and deionized water, while we monitored the voltage over the skin. We found that anodal and cathodal ionotophoresis induced a voltage over the skin that was dependent on the ionic strength of the test solution. The nonspecific vasodilatation during anodal iontophoresis was less pronounced than during cathodal iontophoresis, and was independent of the voltage over the skin. The nonspecific vasodilatation in cathodal iontophoresis was related to the voltage over the skin, and was possibly mediated by depolarization of local sensory nerves. In experiments using cathodal iontophoresis, therefore, the ionic strengths of the vehicle and the drug are important when vasoactive drugs are examined, as the nonspecific vasodilatation needs to be controlled for. As the vasodilatation that we observed was heterogeneously distributed within the area of iontophoresis, LDPI may provide more accurate measurements than conventional laser Doppler perfusion monitoring.