It has previously been shown that opiates produce selective abolition of aversively motivated classically conditioned responses in the rabbit. The experiments reported here show that these effects are mediated by specific activation of opiate receptors within the central nervous system in that this central activation is both necessary and sufficient to produce opiate-induced abolition of conditioned responding. Further characterization suggests that selective activation through opiate-mu-receptor interactions within the periaqueductal gray/periventricular region of the fourth ventricle may be critical in mediating this abolition.