The piriform cortex (PC) is thought to be critically involved in the generation and propagation of forebrain (limbic type) seizures in the rat. The PC extends over a large area at the ventrolateral side of the rat brain with an anterior part highly sensitive for bicuculline-induced and a central part most sensitive for electrically induced seizures. Therefore, distinct parts of the PC might be differentially involved in the generation and spread of seizure activity. Since previous studies indicated that a loss of GABAergic inhibition in the PC is involved in the generation of epileptic activity, we microinjected the GABA-transaminase blocker vigabatrin bilaterally in the anterior, central and posterior PC of previously amygdala-kindled rats and repeatedly tested its effect on kindled seizures. Vigabatrin was anticonvulsant in all groups for up to 13 days with a maximal effect 24 h after injection. However, the anticonvulsant effect on seizure generalization was strongest after microinjection in the central PC suggesting that GABAergic synapses in this part are critically involved in the development of generalized seizures. Since differences in anatomical connections of the PC regions may be responsible for differences in seizure susceptibility, we addressed this question by injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin in different PC subregions. Although there were similarities in the projections from different PC subregions, we also found differences between the PC subregions in their projections to structures known to be important in the limbic seizure network, such as the perirhinal cortex, nucleus accumbens, and striatum. These differences in anatomical connectivity between PC subregions may be involved in the differences in seizure susceptibility observed in the present and previous studies.