With the aim of developing active protection against the noxious effects provoked in humans by scorpion stings, the possibility of eliciting toxin reactive antibodies by immunization with a short peptide was assessed in mice. The amino acid sequence of residues 50 to 59 of Androctonus australis Hector toxin II was chosen, on the basis of previous results indicating that rabbit anti‐(50–59) antibodies neutralize the biological effects of the parent toxin. The peptide was prepared by solid‐phase synthesis procedures and used in different forms (free, linearly polymerized, coupled to KLH, coupled to a low‐molecular weight B‐lymphocyte activator) in order to immunize groups of non‐congenic NMRI or congenic C57BL/6 mice. The reactivities of each serum with the peptide and with the toxin were assessed in ELISA. Strong reactivities with both the peptide (mean titer over 1:52,600) and the toxin (mean titer 1:800) were observed in all mice from the group that received the KLH‐coupled peptide. However, mouse immune sera failed either to recognize the toxin in a liquid‐phase radioimmunoassay or to neutralize the lethal effects of the toxin. The requirements, in terms of affinity and recognition of native conformation, for anti‐peptide antibodies to display neutralizing properties are discussed. © 1992 Wiley‐Liss, Inc. Copyright © 1993 Wiley‐Liss, Inc., A Wiley Company