C3 phenotypes were performed in 90 Caucasian individuals with IgA nephropathy, a common type of chronic glomerulonephritis. The true prevalence of the disease is unknown, since some individuals have clinically inapparent or mild disease and do not undergo the renal biopsy needed for definitive diagnosis. Phenotypes and gene frequencies of the patients, followed at the University of Kentucky and the University of Alabama, were compared with Kentucky native and resident controls and with a larger Caucasian control population. The gene frequency for C3 F was 0.278 for all patients compared to 0.190 for all controls (p<0.01). The C3 phenotype frequencies were similar for Kentucky and Alabama patients. These data indicate that biopsy proven IgA nephropathy patients have a higher frequency of C3 F genes than do healthy controls. The finding could be due to a functional difference in C3 based upon phenotype which predisposes to clinically evident or more severe disease.