The objective of this study was to investigate the relationship between the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) and the response to capecitabine in patients with advanced/recurrent gastric cancer. TP and DPD expression in paraffin-embedded specimens of primary lesions, obtained from 25 patients before capecitabine chemotherapy, were evaluated by immunohistochemical staining with anti-TP and anti-DPD monoclonal antibodies. The patients (19 male and six female) had a median age of 65 years (range 37-74). All had a good performance status [Eastern Cooperative Oncology Group (ECOG) 0 or 1]. Overall response rate to capecitabine therapy was 32%. TP was positive in 19 tumors (76%) and DPD was positive in 13 tumors (52%). The response rate (RR) was significantly higher (Fisher's exact test, P=0.028) in patients with TP-positive and DPD-negative tumors (RR=60%, 6/10) than in the remaining patients (RR=13%, 2/15). TP and DPD expression profiles are useful for predicting a response to capecitabine.