S100 calcium binding protein has been associated with a variety of intra- and extracellular calcium-mediated functions, including learning and memory. We have previously localized S100-immunoreactive neurons correlated with spontaneous discharge activity in the central nervous system of the mollusc, Helix pomatia. In this study, we further investigated the effects of S100 (S100B and S100A1) on electrical discharge activity and membrane currents of Helix neurons, using current- and voltage-clamp techniques. Extracellular application of disulphide-linked S100B (S100B-s-s) in pico- to nanogram/ml concentrations was found to hyperpolarize the membrane resting potential, to inhibit spontaneous discharge activity of action potentials, to alter the stimulus response behaviour from tonic to phasic, to decrease the duration and increase the afterhyperpolarization of action potentials, and to reduce the cell input resistance. Measurement of membrane currents revealed that the total outward current was increased by S100B-s-s. Separation of outward currents showed that three types of potassium currents were altered: (i) an inward rectifying current, (ii) a calcium-activated potassium outward current, both increased by S100B-s-s, and (iii) a delayed, voltage-dependent potassium outward current which was decreased by the protein. The transient potassium outward and the calcium inward currents were not affected by S100B-s-s. Immunocytochemistry showed intracellular labelling of the cytoplasm after extracellular application of the protein, indicating internalization and suggesting an internal site of action. Injection of S100A1 mimicked the effects of S100B-s-s on discharge activity and action potentials. We conclude from our experiments that S100 calcium binding protein, by modulation of potassium currents, may play a role as a neuromodulator in nervous functions.