We have conducted a phase II trial of fludarabine phosphate for advanced measurable adenocarcinoma of the pancreas. The drug was administered every 4 weeks by a daily-times-5 bolus schedule beginning at 20 mg/m2/day. No responses were observed in 20 evaluable patients, 18 of whom were previously untreated. Dose-limiting toxicity was leukopenia, and gastroenterologic side effects were frequent. Life-threatening or fatal renal dysfunction occurred in 3 patients. In this schedule fludarabine phosphate is ineffective against adenocarcinoma of the pancreas and appears to have unpredictable severe renal toxicity.