Anaphylaxis to muscle relaxants appears to be a very useful model to study the IgE-dependent mechanisms of mediator release in humans. The serum IgE binding sites of the drugs appeared to be the ammonium ion determinants. In patients allergic to suxamethonium, one of the most frequently used muscle relaxants for general anesthesia, significant histamine release could be obtained in each case with simple diammonium salts. The length of the chain linking the ammonium groups appears to play an important role. In fact, when the length was less than or equal to 4 A, no significant histamine release could be obtained, whereas the optimal length for histamine release appeared to be greater than or equal to 6 A. Furthermore, muscle relaxants with a rigid backbone between the ammonium determinants (such as pancuronium) are less active than flexible molecules (such as suxamethonium) in initiating mediator release. This study suggests that small divalent molecules can induce anaphylactic shock in sensitized patients and that the length and the flexibility of the chain bearing the haptenic determinants appear to be important factors in the elicitation of mediator release.