Abstract: The interaction between toosendanin (Toes) and botulinus toxin (BoTx) was examined with electron microscope. When Toes (9.0 mg/kg) was injected (sc) to mice and followed immediately or 1 h later by challenge of type A BoTx (1.7 LD 50 per mouse), the ultrastructural changes of NMJ were similar to those seen in the mice treated with Toes alone. The main changes included an obvious decrease in synaptic vesicle number and an increase in elongated vesicle number, In addition, myeloid body or phagosome-like structure can be seen more frequently. When Toes was administrated 5 or 24 h after the challenge of BoTx, however, the average density of synaptic vesicles in areas within 2500 from the presynaptic membrane of NMJ was approximately 90% higher as compared with the average density of synaptic vesicles of the mice treated with Toes alone. The results suggest that once BoTx has already acted on NMJ, it may prevent, in some manner, the vesicle-releasing process evolved by Toes subsequently administerted.