To explore the role of ester groups in the neuromuscular blocking (NMB) property of various quaternary ammonium tropinesters, we have synthesized and pharmacologically evaluated twenty bisquaternary ammonium derivatives where two tropane (I), 3alpha-hydroxytropane (II), or 3-oxotropane (III) moieties were connected on their nitrogen atoms with a polymethylene chain of C3-C12 length. The rank order of potency of these agents in the rat (evoked EMG responses of the ant. tibial muscle) was: I, II, and III. Most potent were the longer chain (e.g. C10-C12) compounds of series I, yet they were inferior to bisquaternary ammonium tropinester derivatives (e.g. N,N'-polymethylene bisquaternary tropinesters, or bisquaternary derivatives of dicarboxylic acid tropinesters). Although some of the agents (series I and II) showed a rapid onset and short duration of action-profile, they also exhibited cardiovascular side effects (e.g. cardiac vagal block and blood pressure changes). In the design of new NMB agents of rapid onset and short duration of action the presence of different ester groups in addition to an azabicyclo ring system (e.g. tropane), seems to be essential.