BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of cyst-filled kidneys. METHODS: In a three-year study, we measured the rates of change in total kidney volume, total cyst volume, and iothalamate clearance in patients with ADPKD. Of a total of 241 patients, in 232 patients without azotemia who were 15 to 46 years old at baseline we used magnetic-resonance imaging to correlate the total kidney volume and total cyst volume with iothalamate clearance. Statistical methods included analysis of variance, Pearson correlation, and multivariate regression analysis. RESULTS: Total kidney volume and total cyst volume increased exponentially, a result consistent with an expansion process dependent on growth. The mean (±SD) total kidney volume was 1060±642 ml at baseline and increased by a mean of 204±246 ml (5.27±3.92 percent per year, P<0.001) over a three-year period among 214 patients. Total cyst volume increased by 218±263 ml (P<0.001) during the same period among 210 patients. The baseline total kidney volume predicted the subsequent rate of increase in volume, independently of age. A baseline total kidney volume above 1500 ml in 51 patients was associated with a declining glomerular filtration rate (by 4.33±8.07 ml per minute per year, P<0.001). Total kidney volume increased more in 135 patients with PKD1 mutations (by 245±268 ml) than in 28 patients with PKD2 mutations (by 136±100 ml, P=0.03). CONCLUSIONS: Kidney enlargement resulting from the expansion of cysts in patients with ADPKD is continuous and quantifiable and is associated with the decline of renal function. Higher rates of kidney enlargement are associated with a more rapid decrease in renal function.