During the last two decades, evidence has accumulated to demonstrate the existence, in the central nervous system, of an endogenous mechanism that exerts an inhibitory control over different forms of epileptic seizures. The substantia nigra and the superior colliculus have been described as key structures in this control circuit; inhibition of GABAergic neurons of the substantia nigra pars reticulata results in suppression of seizures in various animal models of epilepsy. The role in this control mechanism of the direct GABAergic projection from the striatum to the substantia nigra and of the indirect pathway, from the striatum through the globus pallidus and the subthalamic nucleus, was examined in a genetic model of absence seizures in the rat. In this model, pharmacological manipulations of both the direct and indirect pathways resulted in modulation of absence seizures. Activation of the direct pathway or inhibition of the indirect pathway suppressed absence seizures through disinhibition of neurons in the deep and intermediate layers of the superior colliculus. Dopamine D1 and D2 receptors in the nucleus accumbens, appear to be critical in these suppressive effects. Along with data from the literature, our results suggest that basal ganglia circuits play a major role in the modulation of absence seizures and provide a framework to understand the role of these circuits in the modulation of generalized seizures.