The effect of pretreatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), upon the analgesia induced by various doses of 5-hydroxytryptamine (5-HT) was examined in rats and mice. DSP4 treatment (2 X 50 mg/kg, intraperitoneally) of rats caused a complete blockade of 5-HT induced analgesia in the tail-flick, hot-plate and shock titration tests. DSP4 treatment (1 X 50 mg/kg, intraperitoneally) of mice caused a partial blockade of 5-HT induced analgesia in the hot-plate test, but no significant blockade in the tail-flick test. These results are discussed with regard to serotonergic-noradrenergic interactions and the species discrepancy in nociceptive testing.