Small bowel adenocarcinoma (SBA) is a relatively rare disease. Because of its rarity the role of chemotherapy either as adjuvant or for advanced disease has not been clearly defined. Therefore any information, including case reports, is warranted. We report on three patients with adenocarcinoma of the jejunum and ileum. Two patients with positive lymph nodes received postoperative adjuvant chemotherapy with 5-fluorouracil-folinic acid (5FU-FA) for 12 months but they developed metastatic disease 3 and 8 months later, respectively. The third patient was initially treated with the same agents but for metastatic disease. All patients were subsequently treated for tumor recurrence with irinotecan 350 mg/m2 i.v. every 3 weeks as salvage chemotherapy supported by Granulocyte Colony Stimulating Factor (GCSF) for 5 days. Two patients achieved a minor response and had a dramatic improvement of their symptoms. Their survival times after irinotecan administration were 14 and 6 months with an overall survival after primary diagnosis of 29 and 27 months, respectively. The third patient who had a tumor refractory to 5FU-FA progressed also on irinotecan and had an 8-month overall survival. Although conclusions cannot be drawn regarding the role of adjuvant chemotherapy in SBA, it seems reasonable to extrapolate from large bowel carcinoma experience. Irinotecan seems to have some degree of activity in the treatment of SBA but further studies are warranted.