Botulinum and tetanus neurotoxins are water-soluble proteins (mol. wt 150,000) produced by Clostridium botulinum and Clostridium tetani, respectively. It is believed that these neurotoxins, once internalized via receptor-mediated endocytosis, form membrane channels in order to traverse the endosomal membrane and enter the cytoplasm of the nerve terminal. Investigation of the associative properties between neurotoxin molecules could yield an understanding of this channel formation. That is, an association between neurotoxin monomers could result in an oligomeric form of the neurotoxin necessary for assembly of a channel through the hydrophobic interior of the endosomal membrane, thereby allowing passage of the neurotoxin or its active fragment through the resulting pore. Based on the native gel electrophoresis and chemical cross-linking experiments, tetanus neurotoxin exists as a dimer and a trimer, type A botulinum neurotoxin exists as a dimer, trimer, and a larger species, type E botulinum neurotoxin exists as a monomer and dimer, and type B botulinum neurotoxin appears to exist as a dimer in aqueous solution. The results imply that quaternary structures of these neurotoxins may play an important role in their mode of action during neuronal poisoning.