Two patients with acromegaly secondary to ectopic GHRH secretion by metastatic carcinoid tumors were studied before and during therapy with the somatostatin analog octreotide (SMS 201-995). GH and GHRH secretory patterns were assessed during intermittent sc administration, continuous sc infusion (CSI), and continuous iv infusion of octreotide. Octreotide reduced serum GH and plasma GHRH levels in the two patients, although there was differential sensitivity of GH and GHRH. Intermittent sc therapy transiently lowered serum GH in both patients. A higher iv dose was required to reduce plasma GHRH by 50% than to reduce serum GH by 50% (2.0 vs. 0.05 micrograms/kg.h, respectively; patient 1). A similar pattern was found during CSI octreotide administration in the same patient. Chronic therapy with intermittent sc and CSI octreotide was assessed by serial 24-h profiles of GH and GHRH secretion in patient 2. Mean hourly serum GH levels decreased from a pretreatment level of 31.5 +/- 3.5 (+/- SE) to 9.5 +/- 1.5 micrograms/L during CSI therapy (1000 micrograms/day or 0.40 micrograms/kg.h). In contrast, plasma GHRH levels were less effectively suppressed. The mean serum GH levels and the variation in hourly GH values were reduced to a greater extent with CSI than with intermittent sc therapy. Serum insulin-like growth factor I also declined from 5.9 x 10(3) to 2.5 x 10(3) U/L during chronic CSI therapy (patient 2). CSI therapy with octreotide can be more effective than intermittent sc therapy in controlling GH excess in the rare syndrome of ectopic GHRH secretion, although serum GH may not decline to normal.