The molecular mechanism(s) whereby beta, beta'-iminodipropionitrile (IDPN) induces an excitatory behavioral syndrome and a distinct alteration of the axonal cytoskeleton in experimental animals is not known. We demonstrate here that upon intraperitoneal administration to rats, the N-hydroxy analog of IDPN (HOIDPN) induces a parallel spectrum of both neurotoxic effects of IDPN and is approximately 8 times more potent than IDPN in this regard. This is consistent with the involvement of a flavin monooxygenase-mediated N-oxygenation pathway in the toxic activation of IDPN.