The venom of the fish-eating marine mollusc, Conus geographus, contains several neurotoxic peptides having different targets. A novel peptide has recently been isolated from the venom of C. geographus by Drs B. M. Olivera and W. R. Gray and colleagues in our department (in preparation). We report here that this peptide, designated omega CgTX (omega C. geographus toxin), irreversibly blocks nerve stimulus-evoked release of transmitter at the frog skeletal neuromuscular junction. Experiments indicate that the toxin acts by preventing action potential. Consistent with this is the demonstration that omega CgTX also irreversibly attenuates the Ca2+ component of the action potential in dorsal root ganglion (DRG) neurones from embryonic chick. omega CgTX thus provides a unique and potentially powerful probe for exploring the presynaptic terminal.