The potential contribution of dorsal bundle norepinephrine (NE) in the induction of escape disturbances engendered by inescapable shock was evaluated following administration of the NE neurotoxin, DSP4. Treatment with DSP4 produced marked NE reductions in the hippocampus and cortex, a moderate reduction of NE in the locus coeruleus, but only small effects on hypothalamic NE. In contrast to the effect of inescapable shock, DSP4 was found not to influence escape behavior among naive mice or mice that had received inescapable shock. Moreover, DSP4 was without effect on escape performance irrespective of whether animals were individually or group housed, a treatment that has been shown to be sensitive to manipulations that influence escape performance. Treatment with DSP4 was found not to influence the escape interference ordinarily provoked by either haloperidol or alpha-MpT. Interestingly, the escape interference ordinarily engendered by the dopamine-beta-hydroxylase inhibitor, FLA-63, was eliminated among mice that had been pretreated with DSP4. The interference effect induced by inescapable shock is probably not attributable to NE alterations in the hippocampus and locus coeruleus. Serial or parallel effects of shock on more than a single transmitter system are likely to be responsible for the behavioral interference.