The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.