We have recently examined polymorphisms of immunoglobuline heavy chain genes at S mu and S alpha 1 switch region loci by RFLP technique and described differences of genotype frequencies between healthy controls and patients with IgA-nephritis and Henoch-Schönlein-Purpura respectively. In the present study we further characterized the heavy chain constant region of IgG2 and IgG3 and, in addition, a hypervariable region (D 14 S 1) of unknown function localized downstream. In the present larger patient cohort we confirmed a higher frequency of S alpha 1 7.4 kb homozygotes in patients with IgA-nephritis (but not SHP), i.e. 62.0% vs 38.8% in controls, p less than 0.001. Compared to controls RFLP-frequencies of the constant region of IgG2 were also different in patients with IgA-nephritis, but not RFLP frequencies of D 14 S 1 or of the constant region of IgG3. Patients with IgA-nephritis homozygote for 7.4 kb in S alpha 1 had more adverse renal outcome and hypertension and more severe histological lesions (i.e. interstitial fibrosis, p less than 0.005).