Phospholipase A2 (PLA2) in the venom of several poisonous snakes is thought to cause the neuromuscular weakness that can kill someone on the receiving end of a bite. The basis for the neurotoxic activity of PLA2 neurotoxins is poorly defined, partly because it is difficult to experimentally manipulate the neuromuscular junctions they target. Ornella Rossetto and co-workers have now developed a way around this, assessing the effects of these neurotoxins on cultured primary neurons from various regions of the brain (see p. 3561). They demonstrate that four major PLA2 neurotoxins – notexin, β-bungarotoxin, taipoxin and textilotoxin – all facilitate release of glutamate neurotransmitter and induce numerous large bulges to form at synaptic sites. This bulging is accompanied by disruption of the cytoskeleton and redistribution of synaptic vesicle markers such as VAMP2 to the bulges. Rossetto and co-workers propose that it is due to PLA2-induced fusion of synaptic vesicles with the plasma membrane that is not balanced by membrane retrieval. PLA2 activity could promote this both through phospholipid hydrolysis and remodelling of synaptic actin.