OBJECTIVE Blockade of 5-hydroxytryptamine (5-HT)(2A) receptors reportedly mediates or modulates the ability of isoflurane to produce immobility during noxious stimulation and would thereby influence MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimulation in 50% of subjects). However, no data are yet available regarding the role of this receptor in the immobilizing action of sevoflurane. In this study, we examined how prior intraperitoneal administration of either the 5-HT(2A) receptor antagonist altanserin or the 5-HT(2C/2B) receptor antagonist SB 206553 might affect sevoflurane MAC in rats. METHODS Three groups of six male Wistar rats weighing 250-350 g each received one of the following drugs dissolved in dimethyl sulfoxide intraperitoneally 30 min before MAC testing: (1) altanserin 10 mg/kg; (2) SB 206553 10 mg/kg; (3) no drug (vehicle control). MAC was defined as the average of the concentrations that just prevented or just permitted movement in response to clamping the tail for 1 min. RESULTS The rank order of MAC values obtained after intraperitoneal drug pretreatment and sevoflurane exposure was altanserin < SB 206553 < vehicle control. CONCLUSIONS Considering the low levels of 5-HT(2B) receptors within the CNS, this result suggests that 5-HT(2A) and the 5-HT(2C) receptors are present within the neural circuitry influencing sevoflurane MAC. Blockade of 5-HT(2A) and/or 5-HT(2C) receptors may modulate the immobility produced by sevoflurane during noxious stimulation.