We searched for possible immunogenetic markers in SRNS of childhood in 4 different families and children having SRNS. Family A had a boy with SRNS whose father had been treated for childhood SRNS. Family B had 2 first cousin girls and Family C had 2 first cousin boys with SRNS. Family D had a brother and sister with SRNS. HLA-A, -B, -DR antigens were typed, serum C4 and factor B alleles were tested and compared to a group of 30 children with SRNS and a control group of normal individuals. In SRNS the frequency of DRW-8 was 23.5% compared to the normal control 5.9%. DRW-8 was also present in the family with the 2 sibs and 1 family where first cousins had SRNS, but not in the other families. The relative risk of DRW-8 and SRNS measured 5.6. There was a decreased frequency of HLA-BW35 and DRW1, but other HLA-A, HLA-B locus antigens, C4 alleles and factor B alleles occurred in normal frequencies. This report involving families and an unrelated population of children with SRNS failed to find the previously associated increased frequency of DRW-7 and the HLA-B12 nor the increased frequency of relapsing SRNS in children with the factor B-F allele. The significance of genetic haplotyping and completyping in children with SRNS will be discussed and the possible relationship and pathogenesis to an MHC-linked Ir gene.