The synthetic analog of methionine enkephalin, [D-Ala2-Met5]-enkephalin, when administered in vitro to Mytilus edulis ganglia and hemocytes and human peripheral blood lymphocytes, induces the formation of an immunoreactive interleukin-1-like molecule. Additionally, immunoreactive interleukin-1 (IL-1) activity has been found in Mytilus nervous tissue. The stimulatory actions of the extracted immunoreactive IL-1 on Mytilus hemocytes can be antagonized by an IL-1 antibody demonstrating the specificity of the substance. The evidence suggests that the nervous system, via an opioid-IL-1 relationship, can communicate with the immune/defense system through these similar signal molecules. Furthermore, the results indicate that an interleukin-like molecule must have evolved earlier than previously thought.