Six microsatellite markers were selected to detect shifts or loss of heterozygosity (LOH) in urine, serum, and plasma samples of 44 bladder cancer patients. After centrifugation at 15,000 g, we used supernatants for DNA analysis only. Tumor specimens were obtained by transurethral resection (TUR). Genetic alterations were detected in 33 of the 44 bladder tumors (75%). After polymerase chain reaction (PCR), DNA was detectable in 96% of all body fluid samples. Twenty-six percent of the detected microsatellite alterations of free DNA were tumor-specific, but 82% of all microsatellite changes of the tumors could be detected in body fluids. The study indicates that the simultaneous and multiple investigations of highly specific microsatellite markers could have a clinical relevance as a noninvasive tool for diagnosis and screening of bladder cancer. However, new ways for the sensitive DNA isolation of body fluids are needed.