Ten patients with previously untreated acromegaly and invasive pituitary macroadenomas were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz) for 3-30 weeks before transsphenoidal or subfrontal pituitary adenomectomy. Preoperatively, treatment with SMS 201-995 reduced mean 24-h plasma GH concentrations from 8.5-66.7 to below 4.6 micrograms/L in eight patients and by 60-80% in the remaining two patients. Pituitary tumor size decreased 20-54%. Morphologically, the tumors showed decreased total cell, cytoplasmic, and nuclear areas; varying degrees of perivascular fibrosis; and dense granularity. Postoperatively, plasma GH and insulin-like growth factor I concentrations fell into the normal range, and GH dynamics became normal in eight patients. In the remaining two patients mild GH hypersecretion persisted after surgery (mean fasting and random plasma GH, 6.1 and 7.9 micrograms/L), and in one of them GH secretion became normal 1 yr after pituitary irradiation. Thus, preoperative administration of SMS 201-995 consistently induced shrinkage of GH-producing pituitary tumors, and the apparent remission rate was high in the treated patients.