The prognosis of patients with adenocarcinoma of unknown primary (ACUP) is dismal. Various chemotherapy regimens have yielded disappointing response rates and survival. Based on a promising report of Goldberg et al. (J Clin Oncol 1986, 4, 395-399) we performed a phase II study with 5-fluorouracil, adriamycin and mitomycin C (FAM). Only three out of 22 evaluable patients achieved a partial response (14%) for a duration of 22, 30 and 74+ weeks. Median survival was 54+ weeks (range 35-74+ weeks) for responding patients and 33+ weeks (range 9-74+ weeks) for all treated patients. One patient (5%) developed mitomycin C induced hemolytic uremic syndrome. FAM cannot be recommended for routine use in patients with ACUP.