Some regions in the mesencephalon, such as dorsal periaqueductal gray, inferior colliculus and deep layers of superior colliculus have been grouped together as a continuous strip of midbrain structures involved in the integration of the different components of aversive states in the brain. In fact, escape behavior and defensive, or fear-like behavior often result when these sites are electrically or chemically stimulated. Moreover, the behavioral responses induced by stimulation of these structures are, in general, accompanied by increases in mean arterial blood pressure, heart rate and respiration, and by analgesia. Both the behavioral and autonomic consequences of electrical stimulation of the mesencephalic tectum was shown to be attenuated by minor tranquilizers, probably through enhancement of GABAergic neurotransmission. Besides GABAergic interneurons which exert a tonic inhibitory control on neural circuits responsible for the behavioral correlates of the aversion in the above-mentioned structures, several other mechanisms such as opioid, neuropeptides, serotonergic and excitatory amino acids have also been implicated in the regulation of these processes. As to the analgesia that accompanies these aversive states it is mediated by non-opioid mechanisms, particularly by serotonergic ones through 5-HT2 receptors. Now, efforts have been made to characterize the mode of action of these neurotransmitters on their multiple receptors and how they interact with each other to produce or regulate the neural substrates of aversion in the midbrain.