To investigate the relationship between the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and the onset and progression of IgA nephropathy, we studied this polymorphism in 48 patients (21 males and 27 females) with IgA nephropathy and 104 normal controls (51 males and 53 females) using the polymerase chain reaction method. There was no difference in either the genotype or allele frequency of the I/D polymorphism between the patients and normal controls (D allele frequency; 0.303 and 0.325, respectively). But, the mean slope of the reciprocal of the serum creatinine concentration was significantly steeper (p < 0.05) in the patients with the D allele (-0.0104 +/- 0.007 dl.mg-1.month-1) than those without the D allele (-0.0055 +/- 0.008 dl.mg-1.month-1). The mean percentage of the glomeruli with sclerosis or segmental lesions obtained from each renal biopsy specimen was significantly larger (p < 0.02) in the patients with the D allele (49.5 +/- 17.8%) than in those without (33.3 +/- 22.9%). These results suggest that 1. the ACE gene polymorphism is not related to the onset of IgA nephropathy, but 2. the progression of IgA nephropathy may be influenced by the polymorphism which may be involved in glomerular hypertension.