Mutator phenotype of nucleotide repeats has been implicated to be involved in human cancer and other diseases. This type of instability may be the direct result of DNA replication and/or repair errors. To examine mutator phenotype during the development of human prostate cancer, we undertook this study to screen 57 patients with prostatic adenocarcinoma for possible mutator phenotype at 18 microsatellite marker loci on 12 chromosomes (3p, 5q, 6p, 7p, 8p, 10q, 11p, 13q, 16q, 17p, 18q and Xq). Overall, in 37 of 57 patients, we have found positive mutator phenotype in at least one of the loci analysed. A significantly greater number of cases were found to be positive for this phenotype among the poorly differentiated than the moderately- and well-differentiated prostatic adenocarcinomas. Our data suggest that mutator phenotype may play an important role in the development and progression of human prostate cancer.