Octreotide reduces abdominal and vasomotor symptoms in dumping syndrome by unknown mechanisms. Effects of octreotide (50 microgram) on symptoms, hemodynamic parameters and plasma glucose and insulin levels after glucose meals were tested in double-blind, placebo-controlled, crossover fashion in eight patients with dumping syndrome. Gastric scintigraphy tested whether octreotide reduces symptoms by slowing gastric emptying. Octreotide reduced diarrhea, lightheadedness and palpitations after 75 g of glucose, compared with placebo (P < .001). Orthostatic pulse increases after glucose decreased from 36 +/- 6 beats/min after placebo to 9 +/- 5 beats/min after octreotide (P < .05), and standing blood pressure decreases after glucose were abolished (P < .05), but octreotide had no effect on increase in hematocrit or plasma osmolarity after glucose. Late hypoglycemia was prevented by octreotide, and peak fed insulin levels were reduced from 87 +/- 15 to 26 +/- 9 microU/ml after octreotide (P < .05). Times to maximal plasma glucose levels after meals were prolonged from 28 +/- 4 to 78 +/- 6 min after octreotide (P < .05). Octreotide had no effect on gastric emptying of liquids or solids. In conclusion, amelioration of dumping symptoms by octreotide is associated with reduced orthostasis, which is not a consequence of prevention of hemoconcentration. Prevention of late hypoglycemia may be due to blunted insulin release. Octreotide does not reverse rapid gastric emptying, indicating a limited role for this purported mechanism of action.