To evaluate angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism in nephrotic syndrome, 85 patients (minimal-change nephrotic syndrome, MCNS: 55 cases; focal segmental glomerulosclerosis, FSGS: 30 cases) and 61 control subjects were examined. The distribution of ACE genotype in the control group was II 44%, ID 41% and DD 15%. The distribution of ACE genotypes in MCNS was similar to that in controls. However, the distribution of ACE genotypes in FSGS was markedly different from those of MCNS. The DD genotype was more frequent (p < 0.05) in FSGS than in MCNS. Patients with the DD genotype tended to present clinical symptoms at an earlier age. They also showed a lower responsiveness to corticosteroid therapy and a higher incidence of chronic renal failure than those with other genotypes. Our results indicate that the ACE DD genotype in FSGS may be a risk factor for the poor responsiveness to steroid therapy and the development of chronic renal failure.