The SIOP nephroblastoma clinical trials have previously demonstrated that preoperative chemotherapy is advantageous for patients with nephroblastoma (Wilms' tumour). However, some primary tumours increase in size during preoperative chemotherapy, and to investigate the clinical relevance of this progression we studied the patient cohort with increasing tumours included in the SIOP 93-01 study (June 1993 to June 2000). Patients were considered eligible if they had a confirmed localised Wilms' tumour that had been measured in at least two dimensions at diagnosis and before surgery. Tumour response to preoperative chemotherapy was defined according to criteria set by the World Health Organisation (WHO). Patient characteristics in the different response groups were compared and related to event-free survival and overall survival. Patient records were studied regarding compliance with protocol. Tumour progression during preoperative chemotherapy was observed in 57 of 1090 patients (5%) with localised Wilms' tumours. In those cases, the tumours were significantly smaller at diagnosis and were more often stage III (p=0.05) and associated with high risk histopathology (p=0.03). After adjustment for stage and risk group, progression was proved to be correlated with poorer event-free and overall survival (hazard ratio 1.9, p=0.026 and 3.2, p=0.002 respectively). In summary, progression of localised Wilms' tumours is rarely seen in patients during preoperative chemotherapy. However, independent of stage distribution and histopathological risk group, those whose tumours do increase in size have poorer event-free and overall survival.