BACKGROUND: The insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene has been associated with progression of renal diseases. AIMS: We investigated its role in the rate of progression of focal segmental glomerulosclerosis (FSGS). METHODS: Forty-seven patients with end-stage renal disease (ESRD) due to FSGS were evaluated. RESULTS: The distribution of ACE genotype was II-25.5%, ID-55.5%, and DD-19%, as compared to 40 controls with genotype of 7.5%, 60%, and 32.5%, respectively (p= NS). In African Americans (AA) the gene frequencies among patients and controls were I-43%, D-57% vs I-36%, D-64%, respectively. This was different than the gene frequencies in White/Hispanic (W/H) patients I-61.5%, D-38.5% vs I-38.6%, D-61.4%, in controls (P < 0.05). In 22 patients with rapid progression (RP) of FSGS to ESRD the genotype distribution was II-18%, ID -64%, and DD-18%. In 25 patients with FSGS who progressed slowly (SP) the genotype was similar (II-32%, ID-48% and DD-20%, P >0.05). With respect to rate of progression, D allele frequency was similar in AA patients (RP 64% vs SP 50%) and W/H patients (RP 36% vs SP 40%). CONCLUSION: Our study reveals no association between the I/D polymorphism of the ACE gene and the presence of and rapidity progression of FSGS.