Thirty five patients presenting with advanced unresectable digestive tract cancers were treated with high-dose folinic acid (200 mg/m2/d, i.v. bolus) followed by 5-fluorouracil (400 mg/m2 i.v. bolus) on day 2 of uneven courses (day 2, day 58, day 114...). There were 20 colorectal cancers, nine gastric cancers, two oesophageal cancers, two cholangiocarcinomas, one islet cell pancreatic carcinoma and one adenocarcinoma of unknown origin. An objective response was noted in 11/27 evaluable patients (40.7 +/- 19%): four complete and seven partial responses including three of the seven patients who previously failed to respond to 5FU-containing regimen, and eight of the 20 patients who received no prior chemotherapy. Objective responses were encountered in three of the five gastric cancers, five of the 17 colorectal cancers, one oesophageal cancer, one islet cell pancreatic carcinoma and one cholangiocarcinoma. The median duration of response was 6 months and overall median survival was 12 months (range: 1-48). There was one toxic death (non reversible medullar aplasia after the 1st course). This study confirms that this combination is an active regimen both for patients previously resistant to 5FU or untreated patients. It warrants further evaluation (perhaps with continuous 5FU infusions).