Polycystic kidney disease (PKD) is the fourth most common cause of end-stage renal disease and is a common cause of hypertension and associated vascular morbidity. Activity of the renin angiotensin system has been identified as a major component of hypertension and altered fluid and electrolyte physiology in PKD. Activity of this pathway also has been proposed as a potential modulator of structural change in both tubules and the interstitium of the kidney. Cilazapril is a long-acting angiotensin-converting enzyme inhibitor that has been effective in producing vascular remodelling in hypertensive vascular disease. We undertook a study to determine whether therapy with cilazapril would modify the expression of PKD in the Han:SPRD-cy rat, a model of autosomal dominant PKD that closely resembles human disease. Male rats were treated for 4 months, starting at 1 month of age. Control animals were hypertensive by 3 months of age, whereas treated animals were noted to be hypertensive only at the exit assessment (P < 0.001 at 3 months, P = 0.005 at 5 months). At 5 months of age, cilazapril-treated animals had modest but statistically significant reductions in serum creatinine (mean, 1.77 mg/dL v 1.97 mg/dL; P = 0.0006) and morphometrically assessed cyst volume (mean, 0.32 mL v 0.67 mL; P = 0.036). Cilazapril is an effective treatment for hypertension in this model of progressive renal disease and may have benefits beyond the prevention of cardiovascular morbidity.