In a rat model of volume-controlled hemorrhagic shock causing the death of all control animals within 30 min, the intravenous injection of either nicotine (50 μg/kg) or dimethylphenylpiperazinium (DMPP) (0.5 μg/kg) produced a rapid and sustained reversal of the shock condition, with 100% survival 2 h after treatment. Bilateral adrenalectomy completely prevented the anti-shock effect of the two drugs, even though administered at higher doses (150 μg/kg in the case of nicotine; 10 μg/kg in the case of DMPP). It is concluded that stimulation of adrenaline release plays a fundamental role in the mechanism of action of nicotine- and DMPP-induced shock reversal.