We have previously shown that immunoassayable concentration of somatostatin (SRIH) was elevated in 70% of 34 consecutive medullary thyroid carcinoma (MTC) tissue samples. In the present study gastrin releasing peptide (GRP)-like immunoreactivity was measured in tissue extracts from these 34 MTC (25 inherited, 7 sporadic, 2 unclassified) and in 7 normal thyroid tissue. Plasma SRIH, calcitonin (CT) and carcinoembryonic antigen were assayed in all patients. Normal thyroid tissue contained less than 61 pmol GRP per g wet weight; in contrast GRP concentration was elevated (62-7800 pmol/g) in 32/34 tumor extracts. The distribution of tissue GRP values were similar in sporadic as well as in familial MTC. We found no significant correlation between tumor GRP concentration and plasma SRIH (r = -0.05), plasma CT (r = -0.24), or plasma carcinoembryonic antigen levels (r = -0.21). Tumor concentrations of immunoreactive GRP and SRIH were positively correlated when logarithmic transformation was used (P less than 0.01). Thus GRP, as well as SRIH, is a major product of tumoral C cells in human MTC when systematically evaluated in a large number of cases.