Food, drug, and cosmetic dyes of the xanthane type (analogs of fluorescein) were applied to isolated molluscan ganglia and changes in the electrophysiological properties of identified neurons were monitored. The synthetic coloring agents increased the resting membrane potential and conductance of the neurons in a dose-dependent manner by increasing the potassium permeability of the membrane relative to that of other ions. The relative activity of these anionic dyes was highly correlated with their lipid solubility. The structure-activity study of the effects of the dyes on molluscan neurophysiology provides a basis for estimating the toxicity and brain uptake of the dyes in vertebrates, and predicting their effects on metabolism and blood clotting.