The factors that determine the hormone and volume responses of pituitary adenomas to the somatostatin analog octreotide are poorly understood. We, therefore, studied the correlation between 111indium-pentetreotide somatostatin receptor scintigraphy (SRS) and the clinical and immunohistochemical classification of pituitary adenomas, on the one hand, and hormone and volume responses, on the other hand. Ten patients with GH-secreting (6 females and 4 males; age, 31-67 yr) and 14 patients with clinically nonfunctioning (NF) macroadenomas (5 females and 9 males; age, 22-79 yr) were preoperatively treated with 300 micrograms/day octreotide, which was increased to 600 and 1500 micrograms/day at weekly intervals and then continued for at least 3 months until surgery. SRS was performed before therapy. A sellar magnetic resonance imaging scan was performed before therapy; 1, 2, and 3 weeks and 3 months after start of therapy; and after surgery. Acromegalics also had an 8-h GH profile, insulin-like growth factor-I determination, and a 100-g oral glucose load at these time points. An attempt was made to identify NF adenomas as gonadotroph adenomas using their LH, FSH, and alpha-subunit responses to TRH. In acromegalic patients, octreotide suppressed mean GH (8-h profile) and insulin-like growth factor-I concentrations from 34.9 +/- 9.7 to 8.1 +/- 3.6 micrograms/L and from 2122 +/- 1025 to 701 +/- 208 micrograms/L, respectively, after 3 months. Significant (26-85% decline) tumor shrinkage occurred in 5 of 10 patients, mainly within the first week. Tumor shrinkage and GH suppression were not correlated. Four of 7 patients had increased pituitary 111indium-pentetreotide uptake, but this did not predict GH suppression or tumor shrinkage. Of the NF adenomas, 2 responded with shrinkage (57% and 96% decline). Four of 12 adenomas had increased 111indium-pentetreotide uptake, but this did not correlate with tumor shrinkage (2 adenomas; 1 gonadotroph and 1 null cell adenoma), immunohistochemistry, or clinical classification. We conclude that preoperative octreotide therapy suppresses GH in most patients and reduces tumor volume in up to 50% of acromegalic patients. It also induces shrinkage in some NF adenomas, although less frequently. SRS does not predict shrinkage of either tumor type. Shrinkage does not correlate with clinical classification or immunohistological characteristics. Further studies are needed to identify the factors that determine the hormone and volume responses of pituitary adenomas to octreotide therapy.