Abstract Pentylenetetrazol, 1–10 m m, caused reversible hyperpolarization, cessation of spontaneous firing and fall in input resistance of the Retzius cells of leech segmental ganglia. Transient depolarization and increased firing also occurred in the early portion of the response in some cells. The hyperpolarization and input resistance changes occurred in the presence of 20-m m magnesium sulfate, but the early excitatory phenomena never did. Substitution of propionate for chloride in the bathing fluid reduced the hyperpolarization and input resistance change in proportion to the reduction of chloride. In the absence of all external chloride, and with a potassium chloride rather than a potassium acetate electrode in the cell, the drug caused depolarization and increased firing. The typical drug response occurred in the absence of external potassium and the presence of ouabain, 0.1 m m. These data demonstrate that the principal effect of pentylenetetrazol on this particular neuron is a direct, selective, and reversible increase in the chloride permeability of some substantial portion of its membrane. Increased electrogenic ion pumping does not appear to be a significant factor in the response. It is noted that the overall effect of increased chloride permeability in a population of neurons is theoretically quite complex, owing to the fact that the chloride equilibrium potential is negative to the firing level in some cells and positive to it in others.