Symmetrical and unsymmetrical bis-quaternary derivatives of 2-PAM and 4-PAM were synthesized and studied as reactivators in vitro of acetylcholinesterase inhibited by TEPP and DFP. Certain of the 2-PAM-derivatives and all of the 4-PAM-derivatives were far superior to the parent compound in the sense of producing reactivations at lower concentrations. Despite the fact that 2-PAM is much more active than 4-PAM, the bis-quaternary derivatives of the latter were considerably more active in regard to DFP inhibition, but only slightly more active in regard to TEPP inhibition. The best compound with regard to DFP inhibition was the unsymmetrical bisquaternary salt of 4-PAM and pyridine with a pentamethylene linking chain. In general, the addition of extra binding features in these series produced better reactivators.