In humans suffering from polycystic kidney disease (PKD) a gender difference is seen with males exhibiting a faster rate of progression of chronic renal failure than females. The aim of this study was to examine renal function in female rats suffering from autosomal dominant PKD [Han:SPRD (cy/+)] and to look for the occurrence of extrarenal organ manifestations of PKD. In young (2 months) as well as in old female rats (21 months) relative kidney weight was greater in affected than unaffected animals. In contrast, only the old affected female rats developed azotemia (serum urea 95 +/- 124 mg/dl) and severe cystic kidney transformation. Furthermore, old affected female rats exhibited liver cysts (affected 42%; unaffected 3%) and pancreatic cysts (affected 69%; unaffected 15%). Liver cyst epithelia stained positive for cytokeratin 19, a marker for bile duct epithelia. By immunohistochemistry liver cysts exhibited a similar extracellular matrix composition as observed in renal cysts of the same animals (staining positive for laminin, fibronectin and heparan sulfate proteoglycan, but not collagen I). This study proves PKD in the Han:SPRD (cy/+) rat model to be a truly multiorgan disease with a close resemblance of the human disease.