The distribution of calcitonin and calcitonin gene-related peptide (CGRP) has been studied by immunohistochemistry in normal, hyperplastic and neoplastic C cells. Fewer normal C cells contained immunoreactive CGRP than calcitonin, though both peptides can be co-expressed by a single cell. In the hyperplastic C cells that accompany familial medullary carcinoma immunohistochemistry was strongly and diffusely positive for both CGRP and calcitonin. In contrast, in medullary carcinoma, whether sporadic or familial, little CGRP was identified; often only a few strongly positive cells were found in a negative background, while immunoreactive calcitonin was commonly present in large amounts. The findings suggest that CGRP immunohistochemistry may be of value in identifying hyperplastic C cells, and that CGRP levels should be studied in medullary carcinoma families.