BACKGROUND To determine the diagnostic value of plasma DNA microsatellite analysis in patients with transitional cell carcinoma (TCC) of the urinary bladder, by redefining plasma LOH from the equivalent analysis in controls. The method was further tested for MSI (microsatellite instability) and compared with tissue DNA analysis. MATERIALS AND METHODS Sixteen microsatellites were amplified in leukocyte, plasma and tissue DNA from 40 patients and 28 controls, and analysed in a laser-based, capillary electrophoresis system. Plasma LOH was determined from the controls' cut-off values. RESULTS The difference between plasma LOH frequency in patients (25% (10/40)) and controls (14% (4/28)) was not significant. Nevertheless, it occurred significantly more often in low rather than high-grade tumors (p=0.03) and controls (p=0.04). Plasma MSI was dependent upon the number of PCR cycles. Tissue LOH was present in 78% (31/40) of the patients and in none of the controls. Tissue MSI was uncommon. CONCLUSION The results of plasma DNA microsatellite analysis in TCC need cautious interpretation.