The aim of the present phase II clinical trial was to investigate the therapeutic efficacy and tolerance of a combination chemotherapeutic protocol consisting of 4-weekly intervals of 5-fluorouracil, doxorubicin and high-dose methotrexate (FAMeth-regimen) in patients with advanced measurable pancreatic cancer. After a median treatment duration of 4 (2-12) months, one complete and one partial response were achieved in the 13 evaluable patients. Two additional patients had evidence of objective tumour regression, although response was less than 50% of pretreatment tumor measurements. Stable disease was noted in 3 patients, and the tumour progressed in 6. The median survival of all evaluable patients from start of therapy is 7 (2-17) months. Side-effects associated with FAMeth-chemotherapy were generally mild and reversible and primarily included gastrointestinal symptoms (38%) and leukopenia (62%). There was 1 treatment related death due to pancytopenia and sepsis. Our preliminary data suggest some antitumour activity of the regimen against pancreatic cancer, although final assessment of therapeutic results must await accrural of additional patients.