Cysts arising from hepatic bile ducts are a common extra-renal pathology associated with polycystic kidney disease in humans. As an initial step in identifying active components that could contribute to disease progression, we have investigated the protein composition of hepatic cyst fluid in an orthologous animal model of autosomal recessive polycystic kidney disease, heterozygous (BALB/c-cpk/+) mice. Proteomic analysis of cyst fluid tryptic digests using LC-MS/MS identified 303 proteins, many of which are consistent with enhanced inflammatory cell processes, cellular proliferation, and basal laminar fibrosis associated with the development of hepatic bile duct cysts. Protein identifications have been submitted to the PRIDE database (http://www.ebi.ac.uk/pride), accession number 9227.