Studies were performed to investigate the effects of the endogenous opioid peptide methionine enkephalin on experimental metastasis of the murine B-16 melanoma and on murine splenic natural killer cell activity. Methionine enkephalin was shown to significantly inhibit tumor metastasis and significantly enhance splenic natural killer cell activity. These results indicate that the endogenous opioids can modulate the immune response and tumor defense and that methionine-enkephalin may prove to be a beneficial adjunct to the therapy of neoplastic disease.