In previous experiments we have demonstrated that bilateral infusions of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens result in a drastic reduction in the rate of cocaine self-administration. If this effect is due to the destruction of a presynaptic dopaminergic element in this nucleus, then selective removal of the postsynaptic neuron should also disrupt cocaine self-administration. This hypothesis was tested using the neurotoxin kainic acid. Bilateral kainic acid infusions into the nucleus accumbens resulted in a drastic destruction of cell bodies yet did not damage catecholamine innervation in areas anterior to the accumbens. The effects of these kainic acid infusions were evaluated in rats that had previously acquired cocaine self-administration behavior. These lesions were found to severely disrupt cocaine intake and the degree of damage produced in the accumbens was found to correlate (r = 0.88) with postlesion cocaine intake. These lesions were additionally found to disrupt apomorphine and heroin self-administration. The possibility that these results are due to destruction of systems necessary for stimulant and opiate reward is discussed.