Purpose: Because the secretory diarrhea of acute graft-versus-host disease (GvHD) of the gut induces serious metabolic and nutritional disturbances, this study was initiated to assess the use of a somatostatin analogue, octreotide acetate, as adjunctive therapy for severe GvHD of the gut with massive diarrhea. Patients and methods: In a pilot study, six patients with biopsy-confirmed acute gut GvHD after allogeneic bone marrow transplantation received octreotide 50 to 250 μg three times a day subcutaneously. Results: Three of the six treated patients had a prompt and dramatic reduction in stool volume within 1 to 3 days of initiation of octreotide therapy. Conclusions: Somatostatin and its analogues have been used successfully in diarrheal states by antagonism of neuropeptide overproduction, although other potential therapeutic mechanisms include inhibition of fluid secretion, enhanced salt absorption, and inhibition of gut motility. Somatostatin and its analogues may be promising adjunctive agents in the treatment of gastrointestinal GvHD, although assessment in a controlled trial will be required to confirm their therapeutic efficacy.