The expression of three somatostatin receptor subtypes, SSTR3, SSTR4, and SSTR5, was evaluated in 33 pituitary tumor specimens. SSTR3 expression was studied by reverse transcription coupled to polymerase chain reaction, whereas SSTR4 and SSTR5 expression was determined by ribonuclease protection assay. SSTR3 was expressed in 6 of 7 GH-secreting tumors, all 8 clinically nonfunctioning tumors, all 3 prolactinomas, and 1 of 2 ACTH-secreting tumors tested. Eight nonfunctioning adenomas had undetectable messenger ribonucleic acid levels of SSTR4, and only 1 of them expressed SSTR5. SSTR4 expression was also undetectable in 11 GH-secreting tumors, 3 prolactinomas, and 1 ACTH- secreting tumor tested. In contrast, SSTR5 was highly expressed in 10 of 11 GH-secreting adenomas and 1 prolactinoma. Two prolactinomas and 1 ACTH- secreting tumor had low levels of expression of SSTR5. The widespread pituitary adenoma expression of SSTR3, regardless of hormonal secretory type, suggests that SSTR3 might be involved in a somatostatin action(s) other than GH or TSH regulation. SSTR5 is expressed predominantly in mammosomatotroph- derived tumors, suggesting that this receptor subtype may be an important determinant of GH secretion in acromegaly.