We determined the relationship between the gene polymorphism of angiotensin I-converting enzyme (ACE) and the progression of immunoglobulin A (IgA) nephropathy in a large cohort in a multicenter trial of ethnically homogeneous Japanese patients (n = 527). Patients with biopsy-proven IgA nephropathy were recruited from several clinics in Japan. The mean observation period was 8.4 +/- 4.7 years. ACE insertion/deletion (I/D) genotype was determined by polymerase chain reaction amplification using allele-specific primers. Clinical factors investigated in all patients were date of birth, sex, levels of urinary protein excretion, duration of observation, serum creatinine (sCr) level, and creatinine clearance (CCr). ACE genotype distribution did not differ between patients who maintained normal renal function (II, 41%; ID, 44.7%; DD, 14.3%) and those who progressed to renal impairment (II, 41.7%; ID, 40.4%; DD, 17.9%). Kaplan-Meier analysis did not show a significant difference in renal survival rate among the three groups of each genotype. In multivariate analysis, only two variables, proteinuria greater than 1.0 g/d of protein and impaired renal function (sCr >1.2 mg/dL or CCr <70 mL/min) at the time of renal biopsy, were found to be risk factors for disease progression leading to a poor outcome. No association was observed between these variables and ACE genotype. It appears that ACE I/D polymorphism may not affect the progressive deterioration of renal function in patients with IgA nephropathy from our multicenter trial.