Muramyl dipeptide is the smallest biologically active fragment of the lipopolysaccharide (LPS) moiety of gram-negative bacteria cell walls. The present report demonstrates that this product, associated with the immune response to bacterial infection, can modify CNS activity. Specifically, it is demonstrated that 6-0-stearoyl-muramyl dipeptide (MDP) can attenuate opiate withdrawal severity in a dose-dependent fashion when injected directly into areas of the brain essential for this phenomenon. In addition, MDP alters both baseline and postnarcotic electrophysiologic responses of four brain areas essential for various opioid activities. Similar findings have been reported for interferon-alpha (IFN-alpha), a peptide associated with the immune response to virus. Yet, even though MDP and IFN are shown to exert similar effects on opioid activity, there are also some very distinct differences in the actions of both of these immune response products. These observations suggest that central opioid systems may provide targets for the perception as well as the differentiation of afferent immunologic sensory input to the brain.