The present study investigated the action of textilotoxin, isolated from the venom of the Australian common brown snake Pseudonaja textilis, on neuromuscular transmission in isolated toad nerve-muscle preparations. Initial muscle twitch tension experiments revealed a triphasic pattern of changes in muscle tension and a irreversible binding action of textilotoxin (10 micrograms/ml) similar to other snake beta-neurotoxins. This was characterised by an initial depression of twitch tension, followed by a period of enhanced tension, eventually leading to a reduction in tension to complete neuromuscular blockade. These actions on muscle tension were investigated further by assessing the action of textilotoxin on end-plate potential amplitude (EPP). This revealed a similar triphasic alteration of the nerve-evoked release of acetylcholine from the motor nerve terminal. These actions on acetylcholine release were confirmed to be of a presynaptic origin since the modal amplitude of miniature end-plate potentials (MEPPs) was not reduced and in twitch tension experiments the muscle still contracted in response to direct muscle stimulation when nerve-evoked release was completely blocked. Interestingly dramatic effects were observed on the spontaneous release of acetylcholine, including an marked increase in MEPP frequency, a skewing of the MEPP amplitude frequency histogram to the right, and a resultant increase in the number of 'giant' MEPPs. These results indicate that textilotoxin causes a presynaptic blockade of neuromuscular transmission involving a disruption of the regulatory mechanism that controls acetylcholine release.