The novel approach of blunt-end single-strand conformation polymorphism (SSCP) has been applied in the analysis of urine samples from bladder-cancer patients for detecting loss of heterozygosity (LOH) of 3 polymorphic markers in the p53 gene. Of the 28 urine samples examined by SSCP analysis of blunt-ended DNA fragments using a fluorescence-based automated sequencer, 16 were informative in more than 1 of the 3 polymorphic markers at the p53 locus and 8 (50.0%) showed allelic loss of the p53 gene. In analysis of resected tumor tissues, LOH of the p53 gene was detected in 8 of 8 informative samples (100%) with T1 and higher stages and/or Grade 2 and Grade 3 tumors, while it was detected in 6 (75.0%) urine samples obtained from these 8 patients. This new diagnostic modality enables sensitive detection of tumor cells in urine samples and would be applicable for diagnostic bladder cancer with invasive character.