To investigate the genetic determinants for microalbuminuria, we studied an insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene, which influences the plasma ACE level, in 333 consecutive hypertensive patients and 113 normotensive control subjects. The urinary albumin excretion rate was calculated by using a 12-hour urine collection (mean for two consecutive nights from 7 PM to 7 AM) in all 333 hypertensive patients. The ACE D allele frequency did not differ significantly between the hypertensive patients and the normotensive control subjects (0.37 and 0.33, respectively). Among the hypertensive patients, nephropathy (microalbuminuria and albuminuria) was more common (P < .001) in those with the ACE DD genotype than in those with other genotypes. The D allele frequency in the nephropathy group was significantly higher than that in the normoalbuminuric group (0.45 versus 0.32, chi 2 = 10.8, P < .001). These results indicate that ACE I/D polymorphism is a genetic determinant for hypertensive renal disease in hypertensive patients. This polymorphism might be a confounding factor involved in the association between hypertensive nephropathy and cardiovascular events.