The possible existence of an autocrine/paracrine role for SRIF in normal and neoplastic thyroid parafollicular C cells has supported the use of SRIF analogues in the treatment of patients with medullary thyroid carcinoma (MTC). In this study, we have investigated the expression of SRIF by immunohistochemistry and RT-PCR, and the expression of SRIF receptor (SSTR) subtypes by RT-PCR, in a series of 14 MTCs. SRIF messenger RNA was detected in all cases, although immunoreactive cells were only identified in 8. SSTR messenger RNA was present in 12 out of the 14 tumors. Expression of more than 1 SSTR subtype was detected in 10 tumors. SSTR2, the subtype that preferentially binds to the SRIF analogue octreotide, was the subtype most frequently detected, whereas SSTR4 was not detected in any case. These results confirm the frequent expression of both SRIF and its receptors in MTC. The presence of different combinations of SSTR subtypes in a given patient may explain the variable clinical response to SRIF analogues and may promote the search for more selective drugs with different affinities to the various receptor subtypes.