The diagnosis and follow-up of patients with bladder cancer rely on invasive procedures (cystoscopy with biopsy). Polymerase chain reaction (PCR)-based technologies may allow the sensitive detection of cancer-related genetic mutations in exfoliated tumour material, potentially allowing the development of less invasive techniques. This pilot study investigated the feasibility of detecting mutations in exons 5-8 of the p53 gene using single-stranded conformational polymorphism (SSCP) analysis in bladder-washing specimens from patients with bladder cancer. Bladder-washing samples (31) were collected from patients (27) with bladder cancer. An abnormal additional SSCP band was detected in five samples from five different patients suggesting the presence of a p53 mutation. In all five cases the same abnormal SSCP pattern was demonstrated in samples of the corresponding bladder tumour. In one case bladder washings were available from the same patient on two separate occasions with one washing demonstrating a mutation and the other not. In two further cases a mutation was demonstrated in the bladder tumour but not in the corresponding washing. It is concluded that it is possible to detect and characterize p53 mutations in bladder-washing samples from patients with bladder cancer. Improved sensitivity in detecting mutations in a sample containing a mixture of normal and malignant cells may lead to the clinical applicability of molecular methods of disease monitoring.