The involvement of serotonin type-2 (S2) receptors in morphine-induced analgesia was assessed by challenging the effect of 10 mg/kg of morphine sulphate (IP) with the S2 receptor blockers, pirenperone and ketanserin. Tail-flick latencies were assessed at 0, 30, 60, 90 and 120 min after injections by measuring the time that it took each rat to remove its tail from a 52 degrees C water bath. Pirenperone, at 0.08, 0.16, and 0.24 mg/kg (SC) attenuated morphine-induced antinociception. In contrast, only the high 10 mg/kg (SC) dose of ketanserin attenuated the effect of morphine. Because pirenperone easily enters the central nervous system whereas ketanserin does not, these results indicate the involvement of central S2 receptors in morphine-induced antinociception. The 10 mg/kg dose of ketanserin, however, did not attenuate the antinociception produced by 100 mg/kg of ketamine. Thus, the antianalgesic effect of S2 receptor blockers may be specific to opioid-mediated analgesia.