Partial ablation of renal mass initiates a cycle of progressive glomerular injury in the remnant. This process is associated with glomerular hypertrophy, hyperfiltration and systemic hypertension. Congenital deficits in nephron number are also associated with adverse effects on the kidney. Since intrauterine growth retardation is associated with formation of fewer nephrons, the recent observation that low birth weight is associated with increased risk of hypertension in later life raises the possibility that even modest reductions in nephron complement may also predispose to renal injury. Likewise, the numbers of viable nephrons supplied to renal, allograft recipients may be critical determinants of late allograft success or failure, since subsequent acute ischemia and rejection combine to lower the nephron complement to levels akin to the more extensive reductions in renal mass seen in patients with surgical reduction of a solitary kidney, in whom predisposition to hypertension and glomerulosclerosis is evident. This article summarizes recent findings suggesting that congenital nephron endowment is a significant factor in the pathogenesis of chronic renal disease and hypertension.