The localization of immunoreactive calcitonin (IR-CT) in the human gastric mucosa and tumor tissues was studied using an immunohistochemical peroxidase-antiperoxidase method. A small number of IR-CT-containing cells were observed in both infant and adult gastric antral mucosa and the ratio of IR-CT-containing cells to G cells was about 1:50-100. Moreover, tissue content of IR-CT in normal antral mucosa was 2.37 +/- 0.35 ng/g wet weight. IR-CT-containing cells and G cells decreased with the progress of chronic atrophic gastritis and were totally absent in intestinal metaplastic glands. IR-CT was detected in G cells, suggesting a paracrine relation between gastrin and CT. IR-CT was not found in tumor cells of 35 gastric adenomas and 40 well differentiated adenocarcinomas. On the other hand, it was demonstrated in a very small number of tumor cells in 4 of 46 poorly differentiated adenocarcinomas, and in a good number in 3 of 7 scirrhous argyrophil cell carcinomas. IR-CT in plasma could serve, therefore, as a tumor marker of scirrhous endocrine cell carcinoma, and its production in cancer cells was considered to be eutopic rather than ectopic.