In order to analyze renal abnormalities in mice with polycystic kidney disease (PKD), we produced a series of monoclonal antibodies reactive with the murine kidney by hybridizing P3U1 myeloma cells with spleen cells from DBA/2 mice immunized with the kidney of adult-type PKD mice, DBA/2FG-pcy. One clone, D28, reacted specifically with the basement membrane of the proximal tubules of DBA/2 mice and DBA/2FG-pcy mice. It did not react with other parts of the murine kidney nor with other tissues such as the skin, ovary, fallopian tube, testis, lung and small intestine. While other components such as collagen IV, laminin and the core protein of proteoglycan could be found, the D28 epitope could not be found in the basement membrane of renal cysts formed in adult-type (DBA/2FG-pcy) and infant-type (C57BL/6J-cpk) PKD mice. The D28 epitope did not, however, disappear from the basement membrane of proximal tubules in other types of renal abnormalities. These results suggest that the formation of renal cysts in the proximal tubules is associated with an alteration to the proximal tubule-specific structure of the basement membrane. The D28 monoclonal antibody should prove a useful tool with which to analyze basement membrane-associated abnormalities in genetic PKD.