This study describes the characterization of oxylepitoxin-1 (MW 6789), the first postsynaptic neurotoxin isolated from the venom of the Inland taipan (Oxyuranus microlepidotus), which is the most venomous snake in the world. Oxylepitoxin-1, purified using successive steps of size-exclusion and reverse phase-high performance liquid chromatography, produced concentration-dependent (0.3–1.0μM) inhibition of nerve-mediated (0.1Hz, 0.2ms, supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation. Taipan antivenom (5units/ml) prevented the neurotoxic activity of whole venom (10μg/ml), but had no significant effect on oxylepitoxin-1 (1μM). The toxin-induced inhibition of nerve-mediated twitches was significantly reversed upon washing the tissue at 5min intervals. Oxylepitoxin-1 (30–300nM) displayed competitive antagonism at the skeletal muscle nicotinic receptor with a pA 2 value of 7.16±0.28 (i.e. approximately 10-fold more potent than tubocurarine). The venom had a high level of PLA 2 activity (765±73μmol/min/mg) while oxylepitoxin-1 displayed no PLA 2 activity. Partial N-terminal sequencing of oxylepitoxin-1 shows high sequence identity (i.e. 93%) to postsynaptic toxins isolated from the venom of the closely related coastal taipan (Oxyuranus scutellatus scutellatus).