The CD44 cell adhesion molecule is a surface glycoprotein mainly expressed in lymphoid tissues. Recently, abnormal variants of CD44 including alternatively-spliced large molecular variants, have been reported in many neoplastic tissues. We studied the variation in the size of CD44 molecules in 25 transitional cell carcinomas and 11 normal transitional epithelial tissues, using the reverse transcriptase-polymerase chain reaction (RT-PCR) followed by electrophoresis and Southern blot hybridization. Whereas 23 of 25 (92.0%) tumor tissues expressed CD44 splice variants with large molecular size, only 1 of 11 (9.1%) normal tissues expressed the abnormal variants. Urine sediments from 5 of 7 (71.4%) patients also was positive for the CD44 splice variants. CD44 splice variants are increased markedly in human transitional cell carcinoma. In conclusion, detection of CD44 splice variants using the RT-PCR, which is a convenient molecular biological technique, may be useful in combination with other diagnostic methods such as cytology, flow cytometry, and tumor antigens.