In this multi-institutional study of advanced gastric cancer, 141 eligible and evaluable patients were treated with either (a) Adriamycin alone, (b) a combination of 5-fluorouracil, Adriamycin, and methyl-CCNU (FAMe), or (c) a combination of 5-fluorouracil, mitomycin C, and cytosine arabinoside (FMC). In patients with measurable disease and no prior chemotherapy, objective responses were seen in four of 17 patients (24%) receiving Adriamycin alone, in seven of 15 (47%) receiving FAMe, and in three of 18 (17%) receiving FMC. In previously treated patients with measurable disease, objective responses were seen in three of 17 patients (18%) receiving Adriamycin alone and in one of 11 (9%) receiving FMC. In previously untreated patients with both measurable and nonmeasurable disease, FAMe showed a significant advantage over both Adriamycin alone and FMC with regard to interval to disease progression and survival. In comparing Adriamycin alone with FMC in previously treated patients, intervals to disease progression and survival were essentially identical.