Cytotoxic chemotherapy, particularly the regimens that contain 5-fluorouracil (5-FU), can produce diarrhea. Octreotide acetate appears to have a major therapeutic effect in the management of 5-FU-induced diarrhea. A prospective study was conducted to investigate the efficacy of two different doses of octreotide acetate, 100 µg and 500 µg three times daily, for the treatment of severe 5-FU-induced diarrhea refractory to loperamide, and also to evaluate whether the higher dose is more effective in the management of this complication. Fifty-nine patients with tissue-documented colorectal and head and neck carcinoma were enrolled in this study, 28 in the 100 µg arm and 31 in the 500 µg arm of octreotide acetate which was administered s.c. three times daily. Patients were required to have National Cancer Institute Common Toxicity Criteria </= grade 3 diarrhea secondary to treatment with the 5-FU regimen. Octreotide acetate was well tolerated by all patients. Complete resolution of diarrhea was achieved in 17 of 28 (60.71%) patients treated with 100 µg, and in 28 of 31 (90.32%) patients treated with 500 µg of octreotide (p < 0.05). This study suggests a significant benefit in the treatment of 5-FU-induced diarrhea in favor of the 500 µg versus the 100 µg arm. These results support the dose-response effect of octreotide acetate. Even though higher doses of octreotide are more expensive, the cost saved in reduced hospitalization makes the higher dose more cost-effective.