Receptor binding studies demonstrated specific high-affinity, saturable binding of a number of opioid ligands to a wide variety of neural and nonneural human and animal tumors. Radioimmunoassays revealed the presence of beta-endorphin and methionine-enkephalin in these tumors. Both methionine- and leucine-enkephalin were detected in tumor tissue by immunocytochemistry, with immunoreactivity related to the cortical cytoplasm of tumor cells, but not to cell nuclei. Endogenous opioids and receptors were found in benign and malignant tumors representative of ectodermal, mesodermal, and endodermal origin. Receptors and endogenous opioid peptides were present in tumors from many different species, including those transplanted into nude mice. These results suggest that opioid receptors and endogenous opioids are fundamental features of human and animal cancers.