Previous studies have demonstrated that NMDA-dependent, long-term potentiation (LTP) can be induced in both afferent and intrinsic association fiber systems in the piriform (primary olfactory) cortex. In this report we demonstrate that an associative form of LTP can be induced by coactivation of these two systems, which terminate on adjacent apical dendritic segments of pyramidal cells. Potentiating stimulus trains were delivered to either afferent or association fibers, and weak shocks, which were nonpotentiating when delivered alone, were delivered to the other pathway. Under control recording conditions where homosynaptic (single pathway) LTP is consistently evoked, coincident application of these stimuli failed to induce LTP of the weak shock response. However, after local blockade of the fast, GABAA-mediated IPSP, associative LTP was consistently produced in both directions. Induction was blocked by D-2-amino-5-phosphonovaleric acid, indicating that it is dependent on activation of NMDA receptors. It is speculated that afferent and association fibers are segregated on different dendritic segments of pyramidal cells in piriform cortex to allow regulation of associative LTP by way of centrifugal inputs that modulate the activity of GABAergic interneurons.