In addition to being a relay station for auditory pathways in the brainstem, the inferior colliculus may also be part of a brain system commanding defensive behavior. In the present work, we present evidence for the serotonergic modulation of the neural substrate of aversion in this structure. Rats implanted with an electrode-cannula in the inferior colliculus were placed inside a shuttle-box and submitted to a switch-off paradigm. Microinjections of zimelidine, a 5-HT uptake blocker, caused dose-dependent increases in latency and reductions in the frequency of switch-off responses to the inferior colliculus electrical stimulation. The 8-OH-DPAT, a classical 5-HT1A agonist, and alpha-methyl-5-hydroxytryptamine, a highly selective 5-HT2 agonist, injected directly into th e inferior colliculus also produced clear antiaversive effects in a dose-dependent manner. The antiaversive effect produced by alpha-methyl-5-hydroxytryptamine was attenuated by the systemic administration of ketanserin, a preferential 5-HT2 receptor antagonist. These results suggest that serotonergic mechanisms modulate the neural substrates commanding defensive behavior in the inferior colliculus, probably through a cooperative mechanism with the activation of 5-HT1A and 5-HT2 receptors.