Despite extensive resection and systematic lymphadenectomy the prognosis of patients with locally advanced gastric carcinoma remains poor. The effect of preoperative outpatient chemotherapy with etoposide, doxorubicin and cisplatin was evaluated prospectively in 30 patients who had been shown by preoperative staging (including endosonography and surgical laparoscopy) to have gastric carcinoma stages IIIA, IIIB or IV. Haematological side-effects were common and necessitated hospitalization in 13 of 30 patients. Complete clinical response to neoadjuvant therapy was observed in eight of 27 evaluable patients. Resection was performed in 27 of 30 patients, with complete macroscopic and microscopic tumour removal in 24. There were no deaths and no major morbidity following operation. On multivariate analysis complete clinical response (P < 0.01) and complete tumour resection (P < 0.01) were the major independent predictors of long-term survival after neoadjuvant chemotherapy. Actuarial survival after complete tumour removal was superior with neoadjuvant therapy compared with results in an age-, sex- and tumour stage-matched control population who had primary resection (P = 0.07). Recurrence occurred in 17 of 23 evaluable patients who had complete tumour removal, with relapse in the tumour bed or area of lymphatic drainage in 11. These data show that neoadjuvant therapy in patients with locally advanced gastric carcinoma is feasible and appears to increase the rate of complete tumour removal. More powerful and less toxic regimens are, however, required to improve the response rate and to delay or avoid recurrence after neoadjuvant chemotherapy.