Polycystic liver disease is a common manifestation of autosomal dominant polycystic kidney disease. However, factors that regulate hepatic cystogenesis have not been defined, and the effect of cyst formation on hepatic parenchymal mass has not been studied. We validated computed tomographic methods for measuring volumes from computed tomographic images using plastic-agar models and demonstrated that measured volumes were within 10% of actual volumes. The validated methods were used to measure hepatic parenchymal, hepatic cyst and kidney volumes in 25 subjects with polycystic liver disease and nine controls without autosomal dominant polycystic kidney disease. Hepatic cyst volume varied considerably in the 25 subjects with polycystic liver disease (20 to 7,148 ml), but hepatic parenchymal volume was not altered by hepatic cysts and was similar to that of controls (polycystic liver disease vs. controls: 1,357 +/- 185 vs. 1,319 + 340 ml). Total liver volume increased linearly as cyst volume increased (slope = 1.02 +/- 0.05, r = 0.994). Nine of 18 women with polycystic liver disease had massive hepatic cysts (cyst: parenchymal volume greater than 1; range of cyst volumes from 1,354 to 7,148 ml), and the other nine had cyst volumes (20 to 399 ml) similar to men with polycystic liver disease (25 to 1,107 ml). Total kidney volume, a measure of renal cystic disease, did not correlate with either total liver volume or the volume of hepatic cysts. The data indicate that hepatic parenchymal volume is preserved in polycystic liver disease despite massive cystic involvement and that women are uniquely susceptible to massive hepatic cystic disease.