The pathophysiological mechanisms responsible for conduction block in multifocal motor neuropathy (MMN) are still unclear. To clarify the physiological abnormalities at the site of the block, we tested the effects induced by polarizing direct currents on motor conduction along forearm nerves in 25 normal nerves (13 subjects), and at the site of conduction block in six nerves (five patients) with MMN. In healthy controls, whereas nerve depolarization failed to change the conditioned compound muscle action potential (CMAP), hyperpolarization elicited a significant, charge-dependent, decrease in the conditioned CMAP size. Hyperpolarization with 4 mC elicited CMAPs that were 86.76 +/- 5.22% (mean +/- SEM) of the control unconditioned response (P < 0.05). Analysis of individual MMN nerves showed that polarizing currents elicited markedly heterogeneous effects: depending on the nerve tested, depolarization or hyperpolarization in most cases significantly improved conduction along motor fibres across the conduction block. In three MMN nerves, pathophysiological abnormalities were consistent with a hyperpolarizing block, in two with a depolarizing block, and in one with a mixed block. Our observations indicate that the pathophysiological abnormalities at the site of conduction block in MMN may arise from depolarization or hyperpolarization, probably depending on the course of disease.