OBJECTIVE: The purpose of the present study was to investigate the impact of tumour regression and the post-treatment lymph node status on the prognosis of rectal cancer treated by preoperative neoadjuvant chemoradiotherapy. METHOD: One hundred and thirty-five patients with locally advanced T3 and T4 rectal tumours received preoperative long-course chemoradiation, to a dose of 60 Gy external radiation and oral 5-fluorouracil 300 mg/m(2) daily and Leukovorin 22.5 mg/day 5 days a week. Surgery was performed 8 weeks after the end of treatment. The tumour response was evaluated according to the tumour regression grade system and lymph node status in the surgical specimen was assessed. The prognostic value of clinico-pathological parameters was analysed using univariate analysis and Kaplan-Meier methods for comparison of groups. RESULTS: All patients responded to treatment and 47% had a major response, including 25 (19%) complete responders. The median follow-up was 26 months (range 12-94 months). The cancer specific survival was 82% and there was a significant lower survival rate in the group of patients with post-treatment lymph node metastases compared to lymph-node negative patients [63% and 87% respectively (P = 0.007)]. Furthermore patients with a major tumour response and no lymph node metastases in the surgical specimen after treatment had a survival rate of 100% compared with 60% in the group of patients with major response but lymph node metastases after surgery (P < 0.01). CONCLUSION: The combined assessment of lymph-node status and tumour response has strong prognostic value in locally advanced rectal cancer patient treated with preoperative long-course chemoradiation.