Groups of rats were administered either DSP4 (50 mg/kg, ip), xylamine (50 mg/kg, ip), or p-chloroamphetamine (2 X 10 mg/kg, ip), either 2 weeks or 1 week before the testing of two-way active avoidance. DSP4 and xylamine, the selective noradrenaline (NA) neurotoxins, caused a two-way avoidance impairment but p-chloroamphetamine, the selective 5-hydroxytryptamine (5-HT) neurotoxin, did not do so. Pretreatment with desipramine (20 mg/kg, ip) blocked the avoidance impairment caused by DSP4 and xylamine treatment. Neither DSP4 nor xylamine caused any alteration of passive avoidance retention. The biochemical analyses indicated severe NA, but not 5-HT, depletions in the DSP4 and xylamine conditions and drastic 5-HT, but not NA, depletions in the p-chloroamphetamine conditions. These results confirm and extend earlier findings concerning the role of NA in avoidance behavior.