Two cases of gastrin releasing peptide (GRP)-producing medullary thyroid carcinoma are presented. Immunohistochemical examination revealed the presence of GRP-like immunoreactivity (IR-GRP) in the primary tumor tissues. High concentration of IR-GRP was also demonstrated in extracts of the primary tumors by radioimmunologic means with use of a GRP-specific antiserum. Chromatographic analysis showed that the immunoreactivity was composed of at least two molecular forms: one behaved as synthetic porcine GRP on Sephadex G-50 gel filtration and the other as porcine GRP (14-27), a C-terminal active fragment of GRP. The IR-GRP was shown not to be attributed to bombesin-like immunoreactivity. Substance P-like immunoreactivity was not detected in the tumor tissues by either immunohistochemical or radioimmunologic means. This is, as far as the authors are aware, the first finding of IR-GRP as an ectopic product in medullary carcinoma.