A neuromuscular blocking factor has been described in the serum of patients with Miller-Fisher syndrome (MFS). We here examined the effect of immunoglobulins (Ig) on neuromuscular transmission in mice recording quantal endplate currents by means of a perfused macro-patch-clamp electrode. Ig and IgM- and IgG-fractions from an anti-GQ1b-positive patient with typical MFS were highly purified. After application of MFS-IgG, quantal release decreased 1000-fold within 2 min. Returning to control solution the average release came back to the baseline level within 4 min. In contrast, control-IgG and MFS-IgM did not cause any blocking effect. The very fast and fully reversible presynaptic blockade of release caused by the highly purified IgG-fraction may be one factor producing muscle weakness in MFS.