The treatment of advanced gastric cancer is unsatisfactory. The response rates for single chemotherapy agents: 5-fluorouracil, mitomycin-c, methotrexate, cisplatin, adriamycin, nitrosoureas and etoposide are approximately 10-25% and response duration ranges from 3 to 6 months. Complete responses with single agents are rare. Combination chemotherapy produces higher response rates, but these responses are short. Recently the combination of etoposide, adriamycin and cisplatin (EAP regimen) has been reported to produce results superior to what have been previously reported with other regimens. Twenty-four consecutive patients with locally advanced or metastatic gastric cancer (stage III-IV) were treated between June 1990 and December 1992 with the EAP regimen at our Department. Twenty-two patients were evaluable for response and toxicity. Objective responses were observed in 8 of 22 patients (response rate 36%; 95% confidence interval 17% to 59%). No clinical complete response was found. The median duration of the response was 7 months (range 2 to 22). Myelosuppression represented the primary toxicity associated with the EAP regimen. Grade 4 leukopenia was observed in 4 patients (18%). Grade 3-4 thrombocytopenia was registered in two patients, and grade 3 anemia was detected in 4 patients (18%). The median survival for all patients was 8 months and 12 months for the 8 responding patients. The EAP regimen seems to be an effective chemotherapeutic regimen, but cannot be considered the standard therapy for patients with locally advanced or metastatic gastric cancer, because of the high incidence of moderate to severe myelotoxicity and a response rate and duration of survival similar, but not superior, to those obtained using a less toxic schedule.